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Liora

ol the

7

Department of PeJiatric
Ine Harvarcl i^Veaical Ocnool

11

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t

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Gifto/

f

MANUAL

OF

Human Embryology

WRITTEN BY

Charles R, Bardeen, Madison, Wis.; Herbert M. Evans, Baltimore,
Md.; Walter Felix, Zurich; Otto Grosser, Prague; Franz Keibel,
Freiburg i. Br.; Frederic T. Lewis, Boston, Mass.; Warren H. Lewis,
Baltimore, Md.; J. Playfair McMurrich, Toronto; Franklin P. Mall,
Baltimore, Md. ; Charles S. Minot, Boston, Mass. ; Felix Pinkus, Berlin ;
Florence R. Sabin, Baltimore, Md ; George L. Streeter, Ann Arbor,
Mich.; Julius Tandler, Vienna; Emil Zuckerkandl, Vienna.

FRANZ KEIBEL and FRANKLIN P. MALL

IN TWO VOLUMES
VOLUME I

With 423 liluslralions

PHILADELPHIA iS LONDON
J. B. LIPPINCOTT COMPANY

BOSTON MEDIGM. UBRARY

MTHE

FRANCIS A. COUNTWAY

UHMRY Of MEDICINE

COPTKIGHT, 1910
By J. B. LiPPINCOTT COMPAlfT

Printed by J. B. LippincoU Company
The Washington Square Press, Philadelphia, U, S. A,

CONTENTS

PAGE

Preface ix

Introduction xi-xviii

CHAPTER I.

By F. Keibel.
The Germ Cells 1-17

CHAPTER II.

By F. Keibel.
Fertilization 18

CHAPTER III.

By F. Keibel.
Segmentation 19-20

CHAPTER IV.
By F. Keibel.

Young Human Ova and Embryos up to the Formation op the First

Primitive Segment 21-42

CHAPTER V.

By F. Keibel.

The Formation op the Germ Layers and the Gastrulation Problem . . . 43-58

CHAPTER VI.
By F. Keibel.

Summary op the Development op the Human Embryo and the Differ-
entiation OP ITS External Form 59-90

CHAPTER VII.

By O. Grosser.

The Development of the E^g Membranes and the Placenta; Menstru-
ation 91-179

I. Introductiou 91

II. Menstruation 97

III. Observations on Young Ova 103

A. Review of the Descriptions of Young Ova observed in situ ... 105

B. R^um^ of the First Processes of Development up to the For-

mation of the ViUi and the Appearance of the InterviDous

Space 116

V

vi CONTENTS.

C. The Stages from the Appearance of the Villi to their Complete

Formation 127

IV. The Formation of the Placenta; Relations of the Embryonic Mem-
branes up to their Maturity 137

(a) Diflferentiation of the Chorion ; Chorion laeve, Decidua

parietalis and capsularis 137

(b) The Placenta 143

V. The Mature Afterbirth; the Amnion, AUantois, and Yolk Sack up to

Maturity 169

VI. The Uterus post partum 174

CHAPTER VIII.

By F. p. Mall.

Determination of the Age of Human Embryos and Fetuses 180-201

CHAPTER IX.

By F. p. Mall.

The Pathology of the Human Ovum 202-242

CHAPTER X.
By F. Pinkus.

The Development of the Integument 243-291

A. The Epidermis 243

(a) Eariy Stages 243

(b) Further Development 246

(c) Formation of the Stratum Comeum 249

(d) Granule Inclusions of the Epidermal Cells 251

B. The Corium 254

C. The Connection between the Corium and Epidermis 256

D. Dermal Ridges and Folds 257

(a) Dermal Ridges produced by Surface Growth ; Growth Folds 257

(b) Tension Folds 260

E. The Metamerism of the Skin 261

F. The Hair 262

G. The Sudoriparous Glands^ 276

H. The Nails 281

CHAPTER XI.

By C. R. Bardeen.

The Development of the Skeleton and of the Connective Tissues 292-453

Part I. The Histogenesis of the Connective Tissues 293

(a) The Early Mesodermic Syncytium 293

(b) Formation of the Mesodermic Somites 294

(c) The Axial Mesenchyme 296

(d) The Parietal and Visceral Layers of the Mesoderm 296

(e) The Mesenchyme of the Head 297

(f) The Origin of the Connective Tissues 298

Part II. The Morphogenesis of the Skeletal System 316

^ A. General Features 316

^ B. Origin and Fate of the Chorda Dorsalis 327

CONTENTS. vii

C. Vertebral Column and Thorax 331

Regional Diflferentiatioji 341

D. Skeleton of the Limbs 366

Inferior Extremity 367

Superior Extremity 379

E. The Development of the Skull, the Hyoid Bone, and the Larynx . . 398

CHAPTER XII.
By W. H. Lewis.

The Development op the Muscular System 454-*S^

Histogenesis 458

The Segmentation of the Mesoderm 469

The Differentiation of the Primitive Segments 470

The Muscles of the Trunk 473

The Muscles of the Perineum 478

The Ventrolateral Muscles of the Neck 480

The Musculature of the Extremities 482

The Muscles of the Head 505

CHAPTER XIII.
By F. p. Mall.

The Development of the Ccelom and Diaphragm 523-548

The Body Cavities 525

The Septum Transversum 530

The Separation of the Pericardial, Pleural, and Peritoneal Cavities 535

PREFACE

The circumstances that led to the publication of this Manual
of Human P^mbryology, of which the present is the first volume,
have been recorded in the Introductory Chapter, where the aims
of the work are also set forth. A number of German and Amer-
ican embrj^ologists have collaborated in its production, and the
work appears simultaneously in Germany and America. The trans-
lation of the chapters originally written in German has been made
by Professor McMurrich, and the publishers desire to express
their thanks to him for his careful work. The English chapters
have been translated for the German edition by one of the editors,
Professor Keibel. Valuable assistance has been rendered in the
correction of the proofs by Dr. C. Elze, and to him also the thanks
of the publishers are due. The editors desire to express their in-
debtedness to the publishers, Messrs. S. Hirzel, of Leipzig, and
J. B. Lippincott Company, of Philadelphia, for their generosity in
making it possible for the collaborators to enrich the text with
numerous excellent illustrations and for the aid they have ren-
dered in bringing the work to a successful completion.

The second volume will appear at an early date.

Franz Keibel,
Franklin P. Mall.

INTRODUCTION.

By FRANZ KEIBEL, Freiburg i. Br.

Vesal. has rightly been regarded as the founder of human
anatomy. He emancipated anatomy from the dogmas of Galen-
ism and showed that Galen's anatomical observations had really
been made upon apes and that he had attributed to the human body
the structure observed in these forms. Vesal studied the human
body and based his immortal work upon that study. Embryology
, was, however, only incidentally considered by him, and in his stud-
ies in this field he was false to his principles in that, like Galen in
anatomy, he attributed to man what he observed in the embryos
of animals.^

However, the path which Vesal opened in anatomy was also
followed by his successors in embryology. In this connection
Gabriele Fallopia (1523-1562) deserves mention as the first who
gave a correct description of the placenta and of the chorion and
its vessels, and also, on the basis of his own observations, denied
the occurrence of an allantois in man. Bartholomeo Eustachi (d.
1574) studied the development of the teeth in human embryos, and
Julio CaBsare Aranzi (1530-1588) expressly noted that differences
exist between the early stages of development of man and those of
the lower animals. Vesal's successor and pupil, Matteo Realdo
Colombo (d. 1559), endeavored to do for himian embryology what
Vesal had done for human anatomy, promising a consideration of
human embryology and not animal embryology, since Nature had
formed man and animals upon different plans. His efforts, how-
ever, to establish an embryology on the basis of observations on
human material must, as Bloch has pointed out, be regarded as a
failure. And the reasons why Colombo was able to record only
exceedingly incomplete observations are not far to seek. The num-
ber of human embryos accessible to a single investigator in his day
must have been very small ; in addition they were, in part, exceed-
ingly altered pathologically, and, what was still more important,
the phenomena of greatest significance for embryology occur at
such an early period of development that they could not possibly

* Those interested in the history of Embryology are referred to the paper of
Bruno Bloch, Die geschichtlichen Grundlagen der Embryologie bis auf Har^^ey,
Nova Acta Leop.-Carol. Akademie, No. 3, 1904, p. 295 et seq., a work written under
the stimulus and influence of Rudolf Burckhardt.

XI

xii INTRODUCTION.

be observed with the methods of investigation available at that
time. Even in the case of animals these phenomena were still alto-
gether obscure, and almost three hundred years were to elapse
before the necessary preliminary work in this field was accom-
plished. Ulisse Aldrovandi (1526-1605) must first lay a founda-
tion for modern embryology. He was the first to trace systemati-
cally the development of the chick up to the time of hatching
and to give a consecutive account of the development. After
Aldrovandi followed his pupil Volcher Koyter (1534-1600), and
then Hieronymus Fabricius ab Aquapendente (1537-1619). Har-
vey and Malpighi need be only mentioned here, but a few words
may be devoted to the less known Adrian van den Spieghel (Spi-
gelius) (1578-1625).

Spieghel, as may be seen from the introduction to his work
De formate fetu, published the year after his death (1626), had a
clear appreciation of the value of embryology to the physician,
and while his predecessors studied especially the fetal accessory
organs, he turned his attention mainly to the development of the
fetus itself and that of its organs. Since his object was a history
of the development of the human embryo, he was met by the diflS-
culties mentioned above, but where these diflSculties were less pro-
nounced, as in the history of the development of the bones, he
made valuable contributions and materially advanced the investi-
gations of Koyter and Fallopia in this field. In this connection
he made the first attempt at a description based on observation of
the genesis of a tissue, distinguishing those osseous elements which
were formed in preformed cartilage from those which arose in
membrane and describing the growth of membrane bones by the
apposition of osseous spicules at the margins. What Spieghel
had to say concerning the development of the other organs of the
body does not compare favorably with his description of the de-
velopment of the bones, and he also devoted more than half the con-
tents of his book to the consideration of the chorion, the placenta,
and the umbilical vessels ; he recognized the occurrence of an allan-
tois in man. And Spieghel also rendered important service by his
observations on the fetal circulation. In his time the teaching of
Galen that the direction of the blood-stream was the same in both
the umbilical arteries and veins was generally accepted, and with
this false belief it was naturally impossible to obtain a correct
xmderstanding of the fetal circulation. Spieghel, for a number of
good reasons, concluded that the direction of the flow in the umbili-
cal arteries was centrifugal ; he believed, however, that the vessels
<!arried not blood but Galenas spiritus vitalis, and this prevented
him from obtaining a clear idea of the true relations and an
accurate knowledge of the circulation of the blood. The difficulties
which stood in the way of this discovery were exceedingly great,

INTRODUCTION. xiii

and the service rendered by Harvey, as Bloch points out (l. c, p.
333,,^ note), can be rightly appreciated only when, from a study of
the literature, an idea is obtained of how confused were the notions
of even the most distinguished physiologists of the time concern-
ing the movements of the blood.

Without entering into details the names may be mentioned
here of (lualtherus Needham, Nicolaus Hoboken, Nicolaus Steno,
and Thomas Wharton, who rendered services in connection
with the anatomy and physiology of the egg-membranes. The
discoveries of Regner de Graaf, Swammerdam, Hamm, and Leeu-
wenhoek are generally known and have many times been recounted ;
and the much-admired *'Icones Ossiuui Foetus Humani" of Albinus
gave a certain amount of completeness to the knowledge of the
development of the human skeleton. Albrecht von Haller and
Kaspar Friedrich Wolff are worthy of mention for more than the
foimulation of the theories of evolution and epigenesis. Haller
wrote important works on the development of the osseous system
and of the heart, and Kaspar Friedrich Wolff was the founder of
the theory of the germ layers, which was further developed by
DoUinger ^s pupil. Christian Pander, and especially by Karl Ernst
von Baer and Remak. Karl Ernst von Baer finally discovered the
long-sought-for ovum of man and of the mammalia, and is the
real founder of comparative embryology. His work, ^^Ueber
Entwicklungsgeschichte der Tiere, Beobachtung und Reflexion^'
(Konigsberg, 1828 and 1837), must be considered, according to Kol-
liker (** Entwicklungsgeschichte," 1879, p. 14), **the best that em-
bryological literature of all times and all peoples has to show.**
The origLQ of the germ layers and the origin of the organs from
these were now subjected to most careful investigation on all sides
and in all classes of animals. Here Remakes work, which exercised
a very deep and lasting influence, need only be mentioned. The
progress in human embryology did not, however, at first keep pace
with that in comparative embryology. William Hunter's ** Anato-
mia Uteri Gravidi^' (Birmingham, 1774) gave splendid represen-
tations of the egg-membranes and of the gravid uterus, but did
not advance our actual knowledge of embryology, the condition
of which at the close of the eighteenth century can be well under-
stood from the book by D. Ferdinand Georg Danz (^'Grundriss
der Zergliederungskimde des ungebomen Kindes,'' vol. i, EVank-
furt and Leipzig, 1792; vol. ii, Giessen, 1793), which was accom-
panied by annotations by Sommerring, the first authority of that
period. Sommerring himself published in 1799 his '^Icones Em-
bryonum Humanomm,*' which does not, however, contain satis-
factory representations of even the later stages of human develop-
ment, although it is interesting as citing all important earlier
observations. How small was the amount of useful material of

xiv INTRODUCTION.

the early stages of human development accessible even to Karl E.
von Baer can readily be appreciated if one examines the con-
cluding part of his great work, edited by Stieda in 1888. In addi-
tion the methods of satisfactory fixation, of sectioning, to say noth-
ing of serial sections and of reconstruction, were still lacking.
Consequently, the most important early stages in the development
of man remained unknown, and progress even in the case of ani-
mals, of which abundant material was available and could be stud-
ied under the lens while still fresh and transparent, was slow and
diflScult, even when the method of fixing the embryos in alcohol and
dissecting them under the lens with fine needles and knives was
learned. Indeed, it is remarkable what was accomplished in spite
of these arduous and uncertain methods, but results could be ob-
tained only by oft-repeated observations, and, in the case of man,
the material for these was wanting. Thus, we read in Friedrich
Tiedemann's **Anatomie und Bildungsgeschichte des Gehirns im
Fetus des Menschen'^ (Niimberg, 1816) that in embryos of the first
month the place of the spinal cord and brain is occupied by a
clear fluid. His observations begin with an embryo which had
been preserved for some time in alcohol and measured seven lines
in length (from the figure it is to be concluded that Ehenish lines
of 2.18 mm. are meant; the Parisian line corresponds to 2.25 mm.),
that is to say, about 15 mm. Johannes Miiller in his ''Bildungs-
geschichte der Genitalien'' (Diisseldorf, 1830) begins his observa-
tions on human embryos with an embiyo of 8 lines ^ in length
(measurement of the figure gives a length of 20 mm.). What the
younger stages were like could only be conjectured from observa-
tions on animals, and so matters practically remained until His
published his ''Anatomie menschlicher Embryonen.'^ It is true
that human embryos and the egg membranes were extensively
investigated and to a certain extent very well figured at this time —
as in Coste's ''Embryogenie'' (Paris, 1837), in the works of
Pockel (Isis, 1825), Seller (''Die (Jebarmutter und das Ei des
Menschen,*' Dresden, 1831), Breschet ("Etudes anatomiques sur
PcBuf humain," Paris, 1832), Th. L. W. Bischoff ("Beitrage zur
Lehre von den Eihiillen des menschlichen Fetus," Bonn, 1831),
and in the briefer publications of E. H. Weber, Joh. Miiller, R.
Wagner, Von Baer, Wharton Jones, Allen Thomson, and Esch-
richt — ^but the observations remained isolated, they were not suflS-
cient to round out the whole story, and frequently the results failed
to attain completeness owing to a disinclination to destroy a valu-

*"A wonderful human embryo, 3 J lines in length measured along its curva-
ture, with a long-stalked umbilical vesicle and traces of branchial clefts," he could
not sacrifice for investigation; he described it in Meckel's Archiv, 1830. He also
refers to a similar embryo in Meckel's possession (Beitrage zur vergl. Anat.,
vol. i, pp. 71 and 72).

INTRODUCTION. xv

able specimen. The technic of investigation made little progress,
and it is in this particular that His made a change. He had pre-
pared himself by a study of the embryology of the chick and in
connection with this study had worked out a successful technic;
he fixed his embryos, he had constructed an apparatus for section
cutting which, primitive as it now seems, led the way to our
modem microtomes, and he had thought out a method of recon-
struction which has been gradually improved, especially by Born,
into a method that is now absolutely indispensable in embryologicaL
investigation. With this equipment His began the study of human
embryology. Although he was fortunate in obtaining material,
yet this was still scanty, and he was far from imagining that with
it he could study the complete development of man ; but with the
help of the method of reconstruction he first thoroughly worked
out the anatomv of the individual embrvos so far as his technic
permitted, and the results so obtained formed a sure foundation
for human embryology. His models, as well as those he had con-
structed from the chick, were reproduced by Dr. Ziegler in Frei-
burg, and, since these came to be regarded as indispensable by
every anatomical institute, they served, more than anything else,
to increase the knowledge and interest in human embryology.
Gradually the gaps which existed were filled in by His^s own
continued observations and by those of others who studied their
material by similar methods, and in this connection there may be
mentioned the work of Fol, of Phisalix, of Eternod, and, espe-
cially, of Graf Spee. Monographs of individual embryos were
contributed by Piper, Mall, Frederic T. Lewis, Susanna Phelps
Gage, and Bremer, and in connection with the * * Normentaf el zur
Entwicklungsgeschichte des Menschen'^ of Keibel and Elze, to
be considered later, by Thompson, Ingalls, Elze, and Low. In
the meantime the investigation of the individual organ-systems
was not standing still. It was very natural that the foundation
stones upon which certain systems of organs are built up should
be brought together sooner than those of other systems, and, this
happening, His directed his attention to these systems, although
the development of the organism as a whole still remained the
chief object of his thoughts. Thus were achieved the results re-
corded in the third part of his '^Anatomie menschlicher Embry-
onen,'- of which those treating of the general differentiation of
the digestive tract and those concerning the heart may be especially
mentioned. He also published other larger works on the develop-
ment of the nervous system, one of which appeared shortly before
his death.

There should also be mentioned in this connection the work
of A. von KoUiker (eye and olfactory organ) ; of Hammar (the
branchial arch region) ; of Broman, Mall, and Swaen (coelom and

xvi INTRODUCTION.

diaphragm) ; of Hochstetter, Tandler, Erik Miiller, and de Vriese
(vascular system; also Elze) ; of Bardeen (skeleton); of W. H.
Lewis (musculature) ; of Nagel, Keibel, and Bayer (the urogenital
system) ; of the younger His, Hammar, and Streeter (ear) ; and
of the younger His and Romberg (the sympathetic system).

The above enumeration makes no pretence of completeness,
but is merely intended to show how human embryology was ap-
proached from all sides and how the material for a full exposition
of the subject was gradually accumulated.

As has been stated, the idea of working out a complete account
of the development of the human body was always before the mind
of His, but as time went on the hope of accomplishing the task
single-handed failed him; and so he suggested that I should col-
laborate with him in writing a text-book on human embryology.
Unfortunately, the plan was never carried out; I have, however,
gone further with it and prepared the way for its fulfilment by
another work. In the pages of my * ' Normentaf el zur Entwick-
lungsgeschichte der Wirbeltiere'^ I have published, in conjunction
with Curt Elze, a Normentafel for the development of man. In
this I have had the assistance of a large number of other investi-
gators, some of whom, such as Hammar and Tandler, have made
personal contributions, while others have contributed valuable
material, frequently material obtained by operation and most
admirably preserved. Thus I have been able to follow the develop-
ment of the body in an almost perfect series of embrj^os from
about the twelfth day ^ up to the end of the second month and to
obtain many data concerning the first appearance and degree of
development of the organs. An explanation of the stages of de-
velopment earlier than those that I examined had been furnished
by the admirable investigations of Graf Spee and Hubert Peters,*
already mentioned, and the time seemed to me to be propitious
for giving an account of the development of the human body, based
throughout on human material. We have already, it is true, a
whole series of text-books on human embryology, some of them ex-
cellent ; but they are based, for the most part, on other than human
material. They have been written from the comparative embryo-

• According to the age estimate usually employed; if the estimates of Bryce
and Teacher, to which I shall refer later, are correct, the above statement should
be "from about the eighteenth day." (Compare Chapter VIII, The Age of Human
Embryos and Fetuses.)

* Quite recently the observations of Spee and Peters have been confirmed
and extended by Ph. Jung ("Beitrag zur friihesten Eieinbettung beim mensch-
lichen Weibe," Berlin, 1908) ; Bryce, Teacher, and Kerr ("Contribution to the
Study of the Early Development and Imbedding of the Human Ovum," Glasgow,
1908) ; and Frassi ("Ueber ein junges menschliches Ei in Situ," Arch. f. mikr.
Anat., vol. Ixx, 1907, and Weitere Ergebnisse des Studiums eines jungen mensch-
liches Eies in Situ, ibid,, vol. Ixxi, 1908).

INTRODUCTION. xvii

logical stand-point, and, in the interests of continuity, an endeavor
to conceal the gaps in our knowledge is frequently evident. This
will not be the case in the present book. On the contrary, its
endeavor will be to indicate clearly and precisely these gaps, for
thus only can they be filled in; and frequently, as I know, the
material for filling them in is already available. I do not propose,
of course, to dispense with the assistance of comparative embry-
ology and anatomy, but when a gap has been indicated the manner
in which it is probably to be bridged will be pointed out, and,
similarly, attention will be given to those facts of comparative
embryology and anatomy which serve to render intelligible to us
special processes of development in man. As a rule, however, such
considerations will be printed in smaller type, in order that there
may be a clear distinction between facts and deductions. So far
as I can see, all the material necessary for a human embryology,
with the exception of the earlier stages which concern the develop-
ment of the germ layers and the first stages of placentation, is
already available or at least is comparatively readily obtainable.
It would be possible, therefore, to describe the development of all
the organs exclusively from human material if it were possible to
bring together all the material which is now available. If my
colleagues and myself have not succeeded in this, nevertheless
we have been able to approach the goal, and we may hope that it
will fare better with us than with Eealdo Colombo, and even if the
first attempt has not been perfectly successful, the second, whether
made by us or by others, will come so much nearer the goal. The
material is in hand and to be obtained ; it will be brought forward
if we only point out clearly what is lacking.

When working at my Normentafel I had very striking evidence
of the conununitj^ of purpose which to-day inspires our scientific
world. A considerable number of investigators deprived them-
selves for long periods of time of valuable material which they
themselves had not yet had opportunity to study thoroughly, in
order that a larger undertaking might be completed. In the time
of Eealdo Colombo such scientific co-operation did not exist; we
can with pride regard this as a great step in advance. Without
it the completion of such a work as the Normentafel would have
been unthinkable; to-day the post and the telegraph, railways
and steamboats, are at our service and may be turned to the ser-
vice of science. And so it has been possible to bring to completion
such a ** Handbook of Human Embryology ^^ as His had planned
with me in Germany with the assistance of one of his most loyal
pupils on the far side of the ocean, Franklin P. Mall, of the Johns
Hopkins Medical School in Baltimore. It has seemed proper to
Mall and myself to enlist the services of a considerable number of
collaborators, the necessary similarity of treatment being secured

xviii INTRODUCTION.

by the common purpose and by editorial supervision ; in this way
the book would the sooner be brought to completion and, what is
more important, the various chapters would be written with a
complete mastery of the subject. Considered purely objectively
and scientifically the embryology of man has no more interest than
that of any other mammal or vertebrate, and from this stand-point
special endeavors to work out human embryology by itself may
seem to be misplaced. Our interest in the development of the
human body is justified, however, first, by the fact that we are
human beings, and, secondly, because, as Spieghel long ago pointed
out, it is of importance to physicians. That we do not undervalue
the information to be obtained from comparative embryology
and anatomy has already been stated.

HANDBOOK

of

HUMAN EMBRYOLOGY

I,

THE GERM-CELLS.

By FRANZ KEIBEL, Freibueg i. Bb.

The germ-cells of man are the ovmn (oide, ovimn, mature
ovtmi), formed in the ovary, and the spermimn, formed in the
testes. The mature human ovum (the oide of Korschelt and
Heider, the avium of Waldeyer) is not yet known, nor have the
processes which bring about its maturation yet been certainly
observed. Nagel ^ (1888) in connection with his PI. XXI, Fig. 7,
speaks of remains of polar bodies, but this interpretation, as
Waldeyer (1902, in Hertwig's Handbuch, vol. i, part i, p. 333)
has pointed out, cannot be accepted in view of the occurrence in
the ovimi figured of a perfectly unaltered nucleus.

The human ovmn which has reached its full size in the ovary is a true cell,
with cytoplasm, in the ovum termed ooplasm (yolk), a nucleus, frequently spoken
of as the germinal vesicle, and a nucleolus, also termed the germinal spot. In
the nucleus there is, in addition to the nucleolus, a fine, somewhat scanty nuclear
reticulum containing chromatin. We must assume that processes of maturation
occur in such an ovum, similar to those ^ich occur in the ova of other animals.
Briefly stated the maturation consists in that from the ovum, by two rapidly
succeeding divisions, four cells, one large and three small, are formed. The large
cell is the mature ovum, the oide or ovium, the three other cells are the polar
bodies (polocytes), formerly known as the directive corpuscles. At the first
division the first polar body is separated, at the second division the second one,
the first one at the same time also undergoing division. The divisions take place
by mitosis and the final products possess only half the number of chromosomes
characteristic of the ordinary cell-divisions of the species. A reduction of the
number of chromosomes by one-half is thus brought about, but how this reduction
is accomplished and what may be its significance is still a matter of discussion;
indeed, whether the reduction always actually takes place during the nuclear
divisions which produce the polocytes — whether at the one or the other of these
divisions there is really a reduction division — is yet imcertain. For further

*W. Nagel: Das menschliche Ei, Arch. f. mikr. Anat., voL xxxi, 1888.

1

2 HTOIAN EMBRYOLOGY.

consideration of this point reference may be had to Korschelt and Heider,* Haecker,*
Waldeyer,* and E. B. Wilson.' Individually many variations occur in the process;
the diNision of the first polocyte may not take place, the formation of one of the
polar bodies may be suppressed, and, what is noteworthy, modifications occur in
individuals of one and the same species.

The centrosome of the egg-cell seems usually to degenerate during these
processes. The time, with reference to the fertilizaticm, at which the formation of
the polar bodies takes place, varies; the first one is often formed while the ovum is
still in the ovary. In mammals these phenomena have been especially well studied
in the mouse (Sobotta,* Leo Gerlach,' and others), and they have also been investi-
gated in the guinea-pig (Rubaschkin). In man, as has been stated, nothing is
known of these things. We may with perfect certainty assume that polocytes are
formed and that there is a reduction of the chromosomes to one-half the typical
number; but whether variations from the general plan occur, whether or not the
formation of one of the polar bodies is suppressed, we do not know. Similarly we
can say nothing as to the time at which the polocytes are formed. It may be
that the first one is formed while the ovum is still in the ovary, and observations
on this point are much to be desired.

But even although, as is clear from what has just been said,
the mature human ovum is unknown, nevertheless descriptions
have frequently been given of a so-called mature human ovum, that
is to say, of an ovum which was near maturity, and usually the
figure and description given by Nagel has formed the basis of these
accounts. 0. Hertwig follows Nagel's description and Waldeyer
quotes it almost verbally ; it may be given here as well as the figure.

The human ovum retains its transparency in all stages of
development, so that all its anatomical characteristics can be fully
made out in the living object. The cell substance, which may be
termed the ooplasma, and which is frequently spoken of as the yolk,
is separated into two layers. In the inner (central) layer is found
the greater part of the deutoplasm, that is to say, the inclusions
of the ovum, which are usually regarded as nutritive or reserve
substances; they produce merely a slight opacity in comparison
with what is found in the ova of other mammals. The deutoplasm
consists partly of feebly and partly of strongly refractive, finer
and coarser granules; but a distinct delimitation of the deuto-
plasmic elements, such as one finds not only in the ova of the lower
vertebrates but also in those of many mammals, cannot be made
out. The outer layer, the marginal zone of the ooplasma, is much

' Korschelt and Heider : Lehrbuch der vergleichenden Entwicklungsgeschichte,
1902.

'Haecker: Die Chromosomen als angenommene Vererbungstrager, Ergeb-
nisse und Fortschritte der Zoologie, herausgegeben von J. W. Sprengel, vol. i, 1907.

* Waldeyer: Chapter I in 0. Hertwig's Handbuch der vergleichenden und
experimentellen Entwicklungslehre, 1906.

" E. B. Wilson : The Cell in Development and Inheritance, New York, 1906.
'J. Sobotta: Die Bildung der Riehtungskorper im Ei der Maus, Anatom.
Hefte, evi, 1907. The remaining literature is cited here.

* L. (lerlach : Ueber die Bildung der Riehtungskorper bei Mus musculus, Wies-
baden, 1906.

THE GERM-CELLS. 3

more finely granular and transparent. It contains the germinal
vesicle, that is to say, the nuclens of the cell, in which is to be seen
a large germinal spot or nacleolus. In ova examined while fresh
in the liquor follieuli Nagel observed amoeboid movements in the
nncleolus, and such movements have also been described as occur-
ring in the nucleoli of other ova, although Flemming ("Zellsub-
stanz, Kern, und Zellteilung," Leipzig, 1882, p. 157), to whom Nagel
(*'Die weibliche Geschlechtsorgane," in K. von Bardeleben's

Pio. 1.— Afngbovumfromanavariim (omcle of a woman of thirty yun. The aide ot the yirik
upoD which u the nucleua h tovanU the obwrver, eo that out looks direetly down upon the nudeuA and
this nets upon the deuloplum. (From W. Nasel' Arch. f. mikr. Ajiat., vol. mi, 1888, PI. XX, Tit. 6.)

"Handbuch der Anatomie des Menschen," vol. vii, p. 59, 1896)
refers in connection with the egg of Paludina, expressly states that
in spite of many endeavors he had not succeeded in perceiving
changes of form in living nucleoli. Further observations on this
point are much needed. The nucleus appears to be homogeneous
in the freshly stained ovum, but with proper staining a scanty
chromatin network becomes visible. The membrane which encloses
the ovum, the zona pellucida, is remarkably broad and is finely
striated radially. It is separated from the ooplasma by a narrow
perivitelline space and is surrounded by cells, derived from the
cumulus ovigerus which surrounds the ovum in the ovarian follicle.

4 HUMAN EMBRYOLOGY.

These cells form three or four layers, those of the layer nearest to
the zona pellucida having a markedly radiating arrangement and
forming in the fully formed ovum the corona radiata of Bischoff.
This author regarded the corona as an indication of the maturity
of the ovum, a view with which Waldeyer coincides to the extent
that he regards a well-developed corona as a sign of approaching
maturity, without, however, acknowledging it to be an indication of
complete ripeness. In this he agrees with Van Beneden and Nagel.

To this description of the. approximately ripe ovum it must be
added that the existence of a perivitelline space is in dispute.
Nagel believes that the space is of importance in that it permits
a rotation of the ovum so that the nucleus usually lies upon its
upper surface, for this was the position in which he found it in
all fresh, approximately ripe ova. Ebner (Kolliker^s ^'Handbuch
der Gewebelehre, ' ^ vol. iii, p. 517, 1902) disputes both the existence
of a perivitelline space and the assumption that the ovum rotates
witliin the zona pellucida, the nucleus thereby coming to lie upon
the upper surface. He is of the opinion that the nucleus ascends
through the almost fluid ooplasma on account of its lesser specific
gravity, and that the ovum as a whole does not rotate; he bases
his opinion on the fact that when a fresh ovum is burst the greater
part of the ooplasma together with the nucleus is expelled, but the
apparently denser marginal zone of the ooplasma always remains
adherent to the zona pellucida. This could not occur if an interval
jfiUed with fluid was interposed between the marginal ooplasma and
the zona. Furthermore it could be observed, by carefully focus-
sing an equatorial optical section of an uninjured fresh ovum,
that the marginal ooplasma was in intimate contact with the inner
surface of the zona pellucida. **What Nagel figures as a cleft
is a line of refraction, which, with deep focussing, appears to be
in the deeper layer of the yolk (ooplasma), and apparently sepa-
rates the yolk (ooplasma) and the zona, but is really a purely
optical phenomenon which depends on the curvature of the zona
and resembles the line of refraction which one may observe under
similar circumstances in cartilage cavities."

Waldeyer (l. c, p. 332), on the other hand, mantains the cor-
rectness of Nagel 's observation, since he has been able to convince
himself of it from the ovum figured by Nagel. He is not, however,
convinced as to the rotation of the ovtmi within the zona, but agrees
with Ebner that the fact observed by Nagel may be explained by
the ascent of the lighter nucleus through the almost fluid ooplasm.
He himself shows in his Fig. 134 (L c), which is reproduced here
as Fig. 2, an almost ripe human ovum (a fully grown, oocyte), taken
from an ovary while it was still warm, in which there was not the
slightest indication of a perivitelline space. Waldeyer explains
this discrepancy by assuming that the ovum described by Nagel

THE GERM-CELLS. 5

was farther advanced towards maturity. The ooplasm is also
ai-ranged somewhat differently in this ovum from what it is in
that described by Nagel. Close under the zona there is a very
narrow zone of a finely granular material, the ooplasm cortex,
which was clearly seen by Waldeyer as well as by Ebner; beneath
this is a broader, clearer zone of ooplasm in which the nucleus lies
in almost ripe ova, and then comes the central darker mass of the
ooplasm.

Fio. 2.— AJmcMl

: mature human ovum (fully grown oOcyte) taken from an ovary while Btill mn

On the outside appear

■ the epithelium, with the elear •oi.a pellueida; within thi>. a brq~) itratuin

ooplum oiih little yotl

i: and in the oenlre the oflplum rich in yolli. Above to the left, is the nucleue. wii

•ubional nuclei are eeen. XGOO. (After Waldeyer in Uenwis'e Handbueb. v.

i. put i. p. 330. Fi«. 13

4.)

It will be seen that in this connection important questions still
await decision, and if gynaecologists and embryologists work with
a common purpose a solution of them may be expected. Another
question I regard as already settled. The human ovum has no
micropyle, that is to say, no preformed opening in the zona pel-
lucida for the entrance of the spermium. The question as to the

6 HmiAN EMBRYOLOGY.

existence of a micropyle has been recently revived by Holl {Anat
Am., 1891, p. 554; and Sb. K. Acad. Wien., vol. cii, 1893), after
it had long been regarded as settled. It seems to me to be certain
that Holl has been the victim of a mistake. Ebner (Kolliker's
* * Gewebelehre, " vol. iii, p. 518) says **Holl's figure of a section
of an apparently degenerated human ovum shows, traversing the
greatly shrunken zona, a small oblique cleft, probably formed by
accident, perhaps by a wandering cell. True micropyles, so far
as known, traverse the zona radially, not obliquely."

The development of the ovum' will not be discussed here, but
in the chapter on the urogenital apparatus; yet, since it has to do
with the question of the relation of the follicle cells to the ooplasm,
it must be noted here that the mode of formation of the zona pellu -
cida is not yet certain. Waldeyer inclines to the opinion that it is
a product of the ooplasm and is therefore a primary egg-m.em-
brane. E. Hertwig (0. Hertwig's *'Handbuch") and others re-
gard it as a chorion, that is, as a secondary egg-membrane, a
product of the follicle cells; while for others it is a double product
of the follicle cells and the ooplasm, at least so Waldeyer interprets
the observations of Retzius,® Flemming,® and Ebner.^^ According
to these authors there is first formed, from processes extending
from the follicle cells to the ooplasm, a delicate network, which
rests closely upon the surface of the ovum. The network is the
first indication of the zona, and, later, a homogeneous substance
appears between its fibres and forms with them the zona. Whence
this homogeneous substance arises is uncertain; according to
Waldeyer it may come from the ooplasm. A portion of the cell
bridges tliat originally extend between the follicle cells and the
ooplasm are retained in the forming zona substance in a proto-
plasmic condition, but whether such unions persist in the approxi-
mately ripe ovum is uncertain ; certainly their existence can hardly
be reconciled with the presence of a perivitelline space. Kolliker
(according to Von Ebner in Kolliker 's ''Handbuch der Gewebe-
lehre," vol. iii, p. 511) gives the diameter of the approximately
ripe ovum as 0.22-0.32 mm., but Waldeyer remarks {I. c, p. 352,
note) that he has never seen a human ovum of over 0.25 mm. As
regards further measurements Ebner gives the diameter of the
nucleus (germinal vesicle) as 30-45 fi, that of the nucleolus (ger-
minal spot) as 7-10 /A, that of the zona pellucida as 10-11 /a, and
that of the deutoplasm granules (yolk granules. Von Ebner) as
2-3 II.

"Retzius: Zur Kenntnis vom Bau des Eierstockeies und des Graaf'schen
Follikels, Hygiea Festband, Stockholm, 1889.

"Flemming: Zellsubstanz, Kem und Zellteilimg, Leipzig, 1882, p. 35.

**Von Ebner: Ueber das Verhalten der zona pellucida ziun Ei, Anat. Anz.,
vol. xviii, 1900.

THE GERM-CELLS. 7

The production of ova begins at a very early period of life in
the human species. According to Waldeyer (l. c, p. 373; and
^^Eierstock und Ei,'' 1870) at birth or shortly thereafter all the
oogonia have become oocytes of the first order, and so have before
them only further growth and maturation. (The contrary opinion
of Paladino ** I do not consider well founded.) Already in the
ovary of the child the ova may approach ripeness (see C. Hennig;
Ueber fruhreife Eibildung, Sb, d. Leipzig, Naturf. Ges., p. 5, 1878).
Also Waldeyer says, ''One finds in the ovaries of newly-born
and young children follicles the size of a pea with normally devel-
oped ova." On the other hand, those ova which ripen only after
the cessation of ovulation require for their development about fifty
years.

Into the broad field of the pathology of the ovum I cannot enter here; never-
theless, follicles with several ova, multinucleated ova, and the fragmentation of
the ovum may be briefly mentioned. Follicles with several ova may be explained
(Schottlander: Arch, f, mikr. Anat,, vol. xli, 1893; M. and P. Bouin; C, R, Soc.
BioLy vol. lii, p. 17 and 18, Paris, 1900 [dog] ; Ch. Honore: Arch, de Bid., vol. xvii,
p. 489-497, 1900 [rabbit] ) by supposing that the different ova of an egg mass in
the embryo and child have not completely separated, so that several ova have be-
come enclosed within a common follicle wall. They may very naturally tend to the
production of twin pregnancies. They may also be supposed to have arisen by
the fusion of originally distinct follicles. Multinucleated ova have been accounted
for in various ways and perhaps have various methods of origin. They may be
formed by direct nuclear division (Stockel: Arch. f. mikr. Anat., vol. liii, 1899;
Falcone: Monitors zool. ital., Suppl., 1899) or one may suppose that originally
distinct ova have subsequently fused (H. Rabl: Mehrkemige Eizellen und mehreiige
Follikel, Arch, f, mikr. Anat., vol. liv, 1899; S. von Schumacher und C. Schwarz:
Anat. Anz.y vol. xviii, 1900). Finally, they may be produced by the division of
the nucleus of an oogonium, without the corresponding division of the cytoplasm
taking place, as sometimes occurs in spermatogonia. Cases in which several
nuclei occur in an ovum as the result of an imimigration of leucocytes need not be
considered here.

In mammals a division or fragmentation of ripe ova after the expulsion of
polar bodies has been observed (Henneguy, Janosik, H. Rabl, Gurwitsch, Van der
Stricht), and I have also seen such a condition in human ova. The phenomenon
is one leading to the degeneration of the ovum; some authors have compared it
with segmentation and have seen in it a parthenogenetic process, but Bonnet " has
disposed of such notions.

We may now turn to a consideration of the male germ-cell, the
spermium, which is formed in the testis. Tt is well known that for
a considerable time it was uncertain whether the male cells were

"Paladino: La renovazione del parenchima ovarico nella donna, Atti delF
XI Congr. internaz. med. di Roma, vol. ii, Anatomia, 1894, p. 19. Compare also
Arch. ital. de Biologic, vol. xxi, p. 15, 1894; and Monitore zoolog. ital.. Anno V,
p. 140, 1894; also, Per il tipo di struttura delP ovaja, Rendic. Acad. Sc. fis. math.,
Napoli, vol. iii, p. 232, lvS97; also, Sur le type de structure de I'ovaire, Arch. ital.
de Biol., vol. xxix, p. 139, 1898.

"Bonnet: Gibt es bei Wirbeltieren Parthenogenesis? Ergebnisse d. Anatomie
und Entwicklungsgeschichte, vol. ix, 1900.

8

HUMAN EMBRYOLOGY.

not parasites in the seminal fluid — the name spermatozoa is a re-
minder of this idea. The development of the spermium first
-. I clearly showed that this structure is nothing else

f'\ A than a modified cell. Spermatogenesis has also

mm W been studied in man and some figures from

I Meves^^ {Arch. f. mikr. Anat., vol. liv, p. 378) may

I be reproduced here. Other figures have been

I given by Ebner (Kolliker's ^^Handbuch," vol. iii,

p. 454). In the study of human spermatogenesis
attempts have been frequently made to deter-
mine the number of the chromosomes. Dues-
berg, ^^ who also cites the literature bearing on

Fio. 4. — A t^rpical
human spermium,
straightened out. In
o the head is seen from
the surface and in 6
from the edge. In both
figures there are shown
the head cap, the neck
piece with the centro-
somes lying close to the
head, the connecting
piece, and the princi-
pal and end pieces of
the tail. In a is shown
in the anterior part of
the head a dark dot.
( After G.RetEius, Biol.
Untersuchungen, neue
Folge, vol. X, PI. 16,
Figs. 1 and 2.)

Fzo. 3. — Four stages in the spermatogenesis of man. (After Meves, Arch. f.

mikr. Anat., vol. liv, p. 378, 1890.)

the question, finds that in the spermatocytes
there are in all probability twelve. If this be
correct in the spermatogonia and the soma cells
there would be twenty-four, as Flemming had
already (1898) supposed. Good figures of hu-
man spermia have recently been given by Bet-
zius {Biol. Unters., neue Folge x, 1902), and an
excellent diagram by Meves is reproduced by
Waldeyer in Hertwig's ''Handbuch,^' vol. i, p.
146. In the human spermium, which is essentially
similar to that of other mammals, there may be
recognized a head and a tail; a neck piece is not
clearly distinguishable. In the tail, if the indis-
tinct neck piece be disregarded, there are a con-
necting piece, a principal piece, and an end piece.
Seen from the surface the head is oval, and
in side view it is elongated pear-shaped, the tail
being attached to the broader end ; upon each sur-
face of the head there is a slight depression.

'* See, also, Meves : Zur Entstehung der Achsenf aden menschlicher Spemiato-
zoen, Anat. Anz., vol. xiv, 1897 ; and Ueber das Veriialten der Centralkorper bei der
Histog«nese der Samenfaden von Mensch und Ratte, Verb. Anat. Ges. (Kiel), 1898.

"J. Duesberg: Sur le nombre des chromosomes chez Phomme, Anat. Anz.,
vol. xxviii, 1906.

THE GERM-CELLS. 9

According to Waldeyer one sees with very strong magnification
a constriction between the head and the connecting piece, and this
is an indication of the neck; and in this situation Krause and
Waldeyer describe a small depression in the head, which receives
the neck together with the connecting piece. By staining the head
cap can be brought into view, its posterior border marking off an
anterior and a posterior portion of the head. The anterior sharp
border of the cap represents the perforatorium; special perfora-
toria, such as Nelson ^^ and Bardeleben ^® have described, may be
produced by special conditions and perhaps have been confused
with attached bacteria. The neck has the form of a disk, which
is formed by the anterior centrosome bodies, the noduli anteriores
(Fig. 5, A and B, Nd.a, dark), and a homogeneous intermediate
substance, the massa intermedia {Ms.int., clear). The succeeding
connecting piece (pars conjunctionis) begins with the noduli pos-
teriores (the posterior centrosome bodies), represented in the
diagram as a black stripe, and ends with the annulus ; it includes,
therefore, the region of the posterior centrosome, which during
spermatogenesis has divided into these two portions. The filum
principale of the tail traverses the axis of the connecting piece,
extending from the proximal portion of the posterior centrosome.
In this region the filum principale has a delicate investment which
probably passes over posteriorly into the thicker sheath of the
tail and finally ends at the beginning of the filum terminale.
Around this delicate sheath is the spiral sheath, and external to
this the mitochondria sheath. The spiral sheath consists of a
spiral filament, not recognizable in the mature spermium, and an
intermediate substance, the substantia intermedia, represented as
clear in the diagram. The mitochondria sheath is the matrix of
the spiral filament and is characterized by the presence of mito-
chondria granules. At the beginning of the principal portion of
the tail the spiral and mitochondria sheaths terminate, but the
inner thin sheath is probably continued into the involucrum of
the tail. A spiral membrane has been described for the human
spermium by several authors, but does not really occur. The
measurements of the human spermium are, according to W.
Krause ('^Handbuch der menschl. Anat.," vol. i, p. 559, 1876), as
follows : Entire length 52-62 fi, of which the head measures 4.5 /*,
the connecting piece 6 /a, and the tail 41-52 /a. The width of the

"E. M. Nelson: Some Observations on the Human Spermatozoon, Joum.
Quekett Micr. Club, London, ser. 2, iii, pp. 310-314, 1889.

**Von Bardeleben: Ueber die Entstehung der Achsenfaden im menschlichen
und Saugetierspermatozoon, Anat. Anz., vol. xiv, 1897; also, Beitra^ zur Histologic
des Hodens und zur Spermatogenese beim Menschen, Arch, f . Anat. und Entwick-
lungsgesch., Supplementband, 1897; also, Weitere Beitrage zur Spermatogenese
beim Menschen, Jenaische Zeitschrift, vol. xxxi, 1898.

HUMAN EMBRYOLOGY.

^fy

-Fpr

Fio. i

S.

Cd.

Fia. G, A ud B.-

i>.| lo Mev«», Cp
audi (tail); /■.£., p

Diagra

mof >h
<heKl);

(c

lerior bounddry of the connectinj picwl; LJ'.pr., lim«
partis principalia (postenor boundary of the principal por-
tJOD): Pai., pan anlerior apitia (anteriar ponioa of the
bead); Z..Gaf., timM gales (bousdery of tht head up) ; P.p.,

Lli^.

noduli anterioRS (anterior

iTmbM^

■piral filameDl; /nr.. involu

crum (xh.

St.

ment in the tonnetting pie

UilJ; Midi., mitochondria:

"s^l,""

he -piral

aehlechlsKllen, in Hertwig

Handbu

43. A and B.)

THE GEEM-CELLS.

U

head is 2-3 ^ its thickness 1-2 /*. Giant spermatozoa also occur.
Such a structure was figured by Widersperg ^^ in 1885. Since
then abnormal forms of human spermatozoa, after Gt. Betzins "
had described double-tailed forms in 1881, have been recently
specially studied by Ivar Broman.'* Some of his figures are here
reproduced. Fig. 6, o and b, shows a giant and a dwarf sperm;
the tails have in both cases about the normal length. Fig. 6, c and

doubla-buded form.

d, shows double-tailed spermia ; e, one with four tails ; /, a double-
headed one ; and g, a normal sperm under the same enlargement.
Broman remarks that certain forms of abnormal spermia may be
the result of a general weakening of the body by illness and by
the influence of morphine, coffee, and alcohol. The idea of
Bardeleben " that two different forms of human spermia occur

"Gnstav von Widersperg: Beitrage zur EntwicklungsgeEchichfo der Samen-
korper, Areh. f. mikr. Anat., vol. xxv, 1885 (PI. VI, Fig. 18).

"Q. Retzius: Zur Kenntnis der Spermatozoon, Biol. TJntersueh., 1881.

"Ivar Broman: Ueber atypiscbe Spermien (speziell beim Menschen) und
ihre mbglirhe BedeutuDg, mit 107 Abbildungen, Anat. Anz., vol. xzi, p. 455—161,
1902.

"Von Bardeleben: Dimorphism us der mannlichen Oeschlechtszellen bei
Saugetieren, Anat. Anz., vol. ziii. 1897.

12 HUMAN EMBRYOLOGY.

has been disproved, although such a dunorphism occurs among
the invertebrates.

The spermia are motile, being propelled by movements of the
tail. They swim against a current, as was determined indepen-
dently by Roth 21 and Adolphi,^^ although this fact had previously
been observed by Lott (1872) and Hensen (1876), whose results
had been forgotten. The current exercises a directing force upon
the spermia, but for this it must have a certain strength. The
influence begins with currents flowing with a rate of 3-4 ft per
second ; in currents of 4-20 fi the spermia move forward, the more
slowly the more rapid the current ; in a flow of 25 ft they can just
hold their own ; and in more rapid currents they are carried back-
ward. The absolute rapidity of the spermia is 23-26 ft; only at
the beginning of its action does the current increase their activity.
Since dead spermia also move with the head against the current,
the explanation of the effect must be sought in their physical
structure. This adaptation is of great importance for fertiliza-
tion, since it determines that the spermia will direct their course
against the outwardly moving current produced by the cilia of
the uterus and tubes and pass in the most direct route toward the
infundibulum. Waldeyer {I. c, p. 209), following Henle (** Allgem.
Anat.,^' p. 954), makes the rapidity of movement of the spermia
considerably higher than Adolphi; in seven and a half minutes
they cover a distance of 27 mm., this being at a rate of 60 ft per
second.

How long the human spermia may remain motile and capable
of producing fertilization is uncertain. I found still motile spermia
on the third day in the testes of an executed criminal, the organs
having been placed unopened in picro-sublimate ; that they may
remain motile for just as long a period in the cadaver is known
(F. Strassmann, ^'Lehrbuch der gerichtlichen Medizin," p. 61,
1895). Bossies found still living spermia in the vagina twelve to
seventeen days and in the cervix five to seven and a half days
after the last cohabitation; Diihrssen {Sb. Ges. Geburtshilfe tmd
GynaekoL, Berlin, May 19, 1893; also Zweifel: **Lehrbuch der
Geburtshilfe," 3 Aufl., 1902) observed living spermia in a dis-
eased tube nine days after the admission of the patient to the

" A. Roth : Ueber das Verhalten beweglicher Mikroorganismen in stromenden
Flussigkeiten, Deutsche med. Wochenschrift, Jg. 19, p. 351-352, 1893; also, Zur
Kenntnis der Bewegung der Spermien, Arch. f. Anat. und Physiol., Physiol. Abt.,
1904.

" H. Adolphi : Die Spermatozoen der Saugetiere schwimmen gegen den Strom,
Anat. Anz., vol. xxvi, 1905.

** Bossi : fitude clinique et experimentale de Fepoque la plus favorable h la
fecondation et de la vitalite des spermatozoi'des sejoumant dans le nidus seminis,
Rivista di ostetric. e ginecoL, 1891, no. 10, also in Nouv. Arch, d'obstetr. et de
gynecoL, April, 1891.

THE GERM-CELLS. 13

clinic; according to the statements of the patient the last co-
habitation had occurred three and a half weeks previously. Ahl-
feld succeeded in keeping spermia alive for eight days at body
temperature, and Wederhake (*'Zur Technik der Spermaunter-
suchungen," Monatsschrift Urol., vol. x, p. 520-525, 1905) found,
in sperm that had been kept sterile, still living spermia on the
eighth day. All these data indicate that human spermia in the
female genitalia remain still capable of fertilization for a con-
siderable period, certainly over a week. In animals spermia
capable of producing fertilization may remain in the female
genitalia for months, as in the bats, in which, as I have satisfied
myself, copulation occurs in the autumn while the fertilization does
not result until the following April or the beginning of May.

COMPARISON OF THE OVIUM AND SPERMroM.

A comparison of the ovium and spermium is possible only
when the development of both cells is considered. This will be
done in the chapter on the urogenital apparatus and it will be
only briefly treated here. In the development of the male and
female germ-cells three periods may be distinguished. The first
period is that of increase, in which the germ-cells — ^at this stage
termed oogonia in the female and spermatogonia in the male —
undergo a rapid increase by mitotic division. Af a certain period
of development tlie divisions cease and the cells produced by the
last divisions — the oocytes of the first order in the female and
the spermatocytes of the first order in the male — then enter upon
a period of growth, which, especially in the female, leads to
a great increase in size. At the close of this period that of
maturation begins, during which the polocytes are formed in the
female cell. A corresponding period occurs in spermatogenesis.
Two divisions follow quickly on one another; each spermatocyte
of the first order divides first into two spermatocytes of the second
order and each of these again divides into two spermatids. Just
as in the case of the matured ovum, the oide or ovium, and the
three polocytes, which are to be regarded as rudimentary oides,
the chromatin elements are reduced to half their original number,
so too in each of the four spermatids that are formed by the
division of a spermatocyte of the first order the chromosomes are
reduced by one-half. A marked difference, however, occurs:
whereas the four oides (the ovium and the three polocytes) are
very unequal in size, the ovium being many times larger than each
of the polocytes, the four spermatids from each spermatocyte of
the first order are equal in size. And another difference lies in
this, that while the ovium is capable of being fertilized immediately
after or even during the second maturation division, the four
spermatids must still undergo a complicated process of develop-

14

HUMAN EMBRYOLOGY.

ment, that has no equivalent in the ovium; they must be trans-
formed into spermia before they are capable of fertilizing. A
comparison of spermatogenesis and oogenesis is clearly shown by
Boveri's diagram (Fig. 7), taken from Waldeyer (p. 225).

The male and female germ-cells are shown by this comparison
to be essentially equivalent, and yet the subordinate differences
are of the greatest importance. Both are cells in which the nima-
ber of the chromosomes has been reduced to one-half by quite

comparable pro-
f

/\ „ A

A l\ „ A

/I /\ i\ w

,4 A A !\

cesses ; their differ-
ences are associated
with a division of
labor. In the ovum
nutriment is stored
up for the new being
that will be formed;
it consequently grows
to a considerable
size. During the
maturation divisions
all the nutritive ma-
terial is retained by
one cell; the polo-
cytes receive none of
it, the ovium contains
it all. On account of
the mass of nutritive
material the ovium
becomes heavy and is
not in a condition to
move toward a union
with the male germ-
cell ; it must await it.
In the spermatocytes
of the first order
there is, in the first
place, much less nutritive material stored up, and, in the second
place, it is equally distributed among all the four spermatids dur-
ing the maturation divisions ; and, in order that they may be able
to seek out the ovium, each of these four spermatids must be
further modified into spermia. While, therefore, from each
oocyte of the first order but one ovium capable of being fertilized
is produced, from each spermatocyte four spermia arise, and thus
there are formed from an equal number of spermatocytes and
oocytes of the first order four times as many fertilizing spermia
as there are fertilizable oides. And yet this difference, as we

Fio. 7. — Dissram of the development of the primitive germ-
cells (I in the «one of increase) — the primitive sperm cells to the left,
the primitive ova to the right — into spermatids and spermia or into
ovia; II and III in the lone of increase represent the spermato-
gonia and odgonia. The upper small cells in the lone of growth
enlarge to form spermatocytes or oocytes (etO of the first order. By
the division of these cells (I in the maturation sone) there are
formed (to the left) two spermatocytes of the second order (pre-
spermatids) or (to the right) an odcyte of the second order (ei*)
and a first polocyte (psO. The succeeding division, represented at
II in the maturation sone, produces the spermatids (1, 2, 3, 4, to the
left) or a mature ovium (et'), together with the second polocyte
(pt*). A division of pz^ may also take place and then there will be
formed, to the right as well as to the left, four descendants from the
cells represented by I of the maturation lone. (After Boveri and
O. Hertwig, from Walde5rer's *' Geschlechtssellen " in Hertwig's
Handb., vol. i, part i, p. 225, Fig. 55.)

THE GERM-CELLS. 15

shall see later, does not represent, even approximately, the nu-
merical relations of the mature ova and the spermia.

It must be noted, however, that so far as man and the mam-
mals are concerned the comparison of the oogenesis and sperma-
togenesis shown in Boveri's diagram is not quite free from objec-
tion, for it is doubtful if the oogonia and spermatogonia can be
exactly homologized in these forms. For although both arise
from the germinal epitheliimi, nevertheless they appear to belong
to different cell generations. In the male, according to recent
observations, the germ-cells have their origin from cells which
correspond to those of the medullary cords of the ovary; the
ingrowths which give rise to the germinal cords, in which the
ova develop, have no homologue in the testis. The annexed
diagram will make this clear.

Bonnet** imagines that exceptionally the polocytes may also be fertilized
and give rise to embryomata.

As regards the number of germ-cells which may normally
be produced, Hensen estimates that a human female develops in
each ovary about 200 ova ripe for fertilization. Lode^' found
in 1 c.mm. of a human ejaculate 60,876 spermia, and from that
calculates for the entire ejaculate, which averages 3373 c.mm.,
over 200 million spermia, so that during his life a man may
produce about 340 billion spermia* Consequently for every
mature ovium there are about 850 million spermia.

Finally, the question is to be considered whether the sex of
the future individual is in any way determined in the germ-cells,
the ovium or spermium. In the chapter on the development of
the urogenital organs it will be shown that with our present meth-
ods of observation the sex of the human embryo cannot be de-
termined before the fifth or sixth week of development; as is
well known it has been supposed that during the earlier stages
of pregnancy influences may be brought to bear which will de-
termine the formation of the one or the other sex. This, however,
seems to be impossible, since whether the developing organism
shall be of the male or the female sex is, apparently, already
determined at fertilization. This is indicated by the fact that
twins and double monsters formed from a single ovum are always
of the same sex. Most obsen^ers now incline to the belief that
the sex is always determined before fertilization in the ovium, that
there are mature ova (ovia) from which only females and others

••Bonnet: Zur Aetiologie der Embryome, Greifswald. med. Verein, Bericht
in Miinchener Med. Wochenschrift, 1901, p. 315.

"A. Lode: Untersuehung:en Uber Zahlen und R^renerationsverhaltnisse der
Spermatozoiden bei Hunde und Mensch, Arch. f. jjes. Phys., 1891; also, Experi-
nientelle Beitrage zur Physiologie der Samenblasen, Sb. K. Acad. Wiss. Wien.,
Abt. 3, vol. civ, p. 33, 1895.

UUMAN EMBRYOLOGY.

■si

I

THE GERM-CELLS. 17

from which only males can be formed. In my opinion the question
is not yet settled so far as man and the vertebrates are concerned,
but it is certain that in many invertebrates the sex is already de-
termined in the egg. How liie germ-cells of the human female or
male may be influenced so that they will produce either the one or
the other sex has been frequently discussed, but none of the con-
clusions will stand serious criticism. Nussbaum ^^ has shown
that in the rotifer Hydatina senta the sex of the progeny is
determined while they are still within the body of the mother,
since all poorly nourished females deposit eggs from which males
develop, while from the eggs deposited by well-nourished females
only females were formed. All the eggs of any one female pro-
duce the same sex and neither fertilization nor any treatment after
fertilization has any effect. In an extensive series of observations
on a mammal, the mouse, 0. Schultze^^ did not succeed in influ-
encing the sex character ; no influence was exerted by the age or the
difference of age of the parents, by the age of the sexual products,
by in-breeding or by incest-breeding, by sexual appetency, etc.
For further consideration of the question reference may be made
to Henneberg ^^ and Lenhossek.^®

^ M. Nussbaum : Die Entstehung des Geschlechts bei Hydatina senta, Arch,
f . mikr. Anat., vol. xlix, p. 227-308, 1897.

" 0. Schultze : Zur Frage von den geschlechtsbildenden Ursachen, Arch, f .
mikr. Anat., vol. Ixiii, p. 197-257, 1903.

**B. Henneberg: Wodurch wird das Geschlechtsverhaltnis beim Menschen
und bei den hoheren Tieren beeinflusst? Ergebnisse der Anat. und Entwicklungs-
gesch., vol. vii, p. 697-721 (Lit., 1897), 1898.

*M. von Lenhoss^k: Des Problem der geschlechtsbestimmenden Ursachen,
Jena, 1903.

Vol. I.— 2

II.

FERTILIZATION.

By FRANZ KEJBEh, Freiburg i. Br.

Nothing is known concerning the fertilization of the hnman
ovnm, but it may be presumed that it takes place in essentially the
same maimer as in other mammals, and for an account of the
process in these forms reference may be had to the works of
Sobotta and Leo Gerlach, cited in the preceding chapter. The
usual place for fertilization must be the first portion of the tube.
That the spermia penetrate into the tube has been observed
(DiLhrssen: Sb. d. Ges. f. Gyn. und Geburtsh. in Berlin, 1893; and
Zweifel: ^^Lehrbuch der Geburtshilf e, " 3 Aufl., 1902), and is
also made certain by the occurrence of tubal pregnancies. Occa-
sionally the union of the ovum and sperm-cell may take place upon
the surface of the ovary or even in the interior of the Graafian
follicle, as is definitely shown by rarely occurring cases of ovarian
pregnancy (see Freund and Thome,^ and Bryce, Teacher, and
Kerr 2). Accurate estimates of the rapidity of penetration of
the spermia into the uterus and tubes are not available, but
it may be supposed that in one or two hours after coitus the
spermia have penetrated far into the tubes. That fertilization
of the ovum may take place after it has reached the uterus seems
to me from observations on other mammals very improbable; at
all events no good grounds for such a supposition seem to exist.
Nevertheless Wyder^ regards the uterus as the normal site of
fertilization; and other gynoBCologists — Hofmeier, for example —
agree that fertilization may occasionally take place in the uterus.
Waldeyer also comes to this conclusion and states (Hertwig's
* * Handbuch, ^ ' vol. i, p. 370) that, '^It cannot be denied, however,
that under certain circumstances fertilization may first occur in
the uterus"; he does not state, however, what these circumstances
may be.

*H. W. Freund and R. Thome: Eierstoekschwan<2:erschaft, Virch. Arch.^
vol. clxxxviii, pp. 54-91.

*Br\Te, Teacher, and Kerr: Contributions to the Study of the Early Develop-
ment and Imbedding: of the Human Ovum, Glas^w, 1908.

'Th. Wyder: Beitra^ zur Lehre von der Extrauterinschwangerschaft und
dem Orte des Zusammentreffens von 0\'ulum und Spermatozoen, Arch. f. Gynakol.»
vol. xxviii, 1886.

18

III.

SEGMENTATION.

By FRANZ lOEIBEL, Freiburg i. Br.

The segmentation stages of the human ovum have not yet
been observed. We may with certainty assume that the early
stages of fertilization are passed through during the passage of
the ovum through the tube, but whether the entire segmentation
takes place during this passage, or in what stage of seg-
mentation the ovum reaches the uterus, cannot even be con-
jectured. In mammals there are apparently differences in this
respect. The time, also, that the human ovima requires for
the passage of the tube is very diflScult to estimate; accord-
ing to the data obtained from other manunals it cannot well
be believed that the uterus is reached before the fifth day.
Similarly, it is unknown whether the ovum becomes imbedded
in the mucous membrane immediately after it has reached
the uterus. That it is possible by good fortune and persistency
yet to observe segmenting human ova in the tube is shown by the
observations of Letheby ^ and Hyrtl (in a work by Bischoff ^ and
in Froriep's '* Neue Not.," 1852, No. 603), who discovered ova in
the tube, althouja:h they were not able to make observations
of the segmentation, partly on account of the imperfections of
their technic and partly because the ova were unfertilized. The
relative certainty with which experienced embryologists are able
to-day to obtain the segmentation stages of even large mammals is
an encouragement for further efforts in this direction. The force
which propels the ovum through the tube into the uterus is the
ciliary action of the tubal epithelium, and injury to this epithelium
mav be the cause of the retention of the ovum in the tube or in
a diverticulum of it and so the cause of a tubal pregnancy. If
the ciliary current is not impaired, the ova are readily driven over
any diverticula that may exist (Kromer^).

*H. Letheby: An Account of Two Cases in which Ovules or Their Remains
Were Discovered in the Fallopian Tubes of Unimpregnated Women who Had
Died during the Period of Menstruation, Philos. Transact. Royal Soc. London,
1852 (altogether unsatisfactory). See also J'roriep's Neue Notizen, 1852, No. 603.
' Th. L. W. Bischoff : Beitrage zur Lehre von der Menstruation und Bef nich-
tung, Zeitschrift fiir rationelle Medizin, neue Folge, vol. iv, 1854.

P. Kromer: Untersuchungen iiber den Bau der menschlichen Tube, Leipzig,
1906.

19

20 HUMAN EMBRYOLOGY.

It may be r^arded as quite eertaia not only that the human ovum nndergoes
a seg^iientation quite similar to that of the other mammals, but also that it is a
Becondary total segmentation. The ancestors of the hnmau species, like those of
other mammals, must have once possessed yolk-laden meroblastic ova. A separation
of the segmentation cells according to their developmental potencies has been
variously postulated for the earlier stages of the
mammalian segmentation, but conclusive evidence
for this is lacking, the observations hitherto made
not being capable of such an interpretation. This
is true also of the observations which have been
supposed to indicate the existence of a gastndatiou
process in the later stages, but this question will
be considered in the chapter dealing with the forma-
tion of the germ layers and the gastrulation prob-
lem. Finally, it may be noted here that Hubrecht
has recently succeeded in finding the ovum of a
Tig 9— Ovum of ■ monker monkey in segmentation. It has been figured in
ia KsmeDtatioD. from the tuba of the posthumous paper by Selenka which I have
X wo^Tf^^i^^^"^': *^'^ (" MenschenafEen," 5 Lief., Zur vergleich-
■oheomfrea," G Lief., Fi(. 1, p. 331, endou Kcimesgeschichte der Primaten, Wiesbaden,
>»03.) 1903) and is reproduced here (Fig. 9), since it is

the only primate ovum in a segmentation stage
at present known. Selenka states ooneeming this ovum, which was found in
serial sections of a tube of a MacatMa nemestrinwa from Java: "At- about the
middle of the oviduct was the ovum, having a diameter of 0.04 mm. and loosely
attached to the somewhat frayed out ciliated cells. The largest of the approximately
ripe ovarial ova were of about the same size. Four segmentation cells of about
equal size are clearly to be distinguished; two of these (the central and left
upper ones in the figure) are irregularly oval, the other two are almost spherical.
The cells are naked; no trace of an enclosing membrane is to be observed.
The shrinkage which tie tissues of the oviduct show suggests the idea that the
segmenting ovum no longer retains its natural condition. It is, however, of
importance to note what the preparation reveals: The segmentation begins in a
manner rimilar to that of other higher mammals, and it is probable that it is com-
pleted as soon as the ovum has entered the uterine enlat^;ement" This last
conclusion I cannot accept.

IV.

YOUNG HUMAN OVA AND EMBRYOS UP TO

THE FORMATION OF THE FIRST

PRIMITIVE SEGMENT.

(a CBITICAl. account)

By FRANZ KEIBEL, Freiburg i. Br.

By the term ovum is understood in human embryology not
only the egg-cell but also later the entire structure developed from
the egg-cell, the embryo or fetus surrounded by the amnion and
chorion. In this sense the word is used here. I do not intend to
enumerate and describe here all young and very young human ova
that have been observed, but only those which may be regarded
as normal or approximately so, and as such I can regard only
those in which an embryo has been observed. The observations of
Graf Spee and Peters on human ova, and of Selenka on those of
monkeys, have shown that in man and the primates the chorion
grows much more rapidly than the embryo, that, consequently, a
relatively large ovum may contain a very small embryo, and that
even in the youngest ova yet studied the amnion and the yolk
sack are already formed. I shall show later that in all probability
the embryo never lies free upon the surface of the ovum, as it does
in the birds and in many mammals, but that from the beginning
it is sunk in the interior of the ovum, and that the amniotic cavity
arises as a cleft and not by the formation of folds, and is always
closed. The extraordinary minuteness of the embryonic anlage
is a sufficient explanation why in early times, when the methods
of investigation were imperfect, it was overlooked or unrecog-
nized ; many of these earlier described ova may have been normal
or nearly so. But when no embryonic anlage is found in an
ovum that has been investigated according to all the rules of
modern technic, as is the case with that which G. Leopold ^ has
lately studied with so much care, that ovum is certainly to be
regarded as pathological; and the occurrence of maternal blood
in the interior of the ovum is further evidence in this direction,
as Spee has pointed out in Schwalbe's Jahresbericht. Leopold's

* G. Leopold : Ueber ein sehr junges menschliches Ei, Arb. Kgl. Frauenklinik,
Dresden, vol. iv, Leipzig, 1906.

21

22 • HUMAN EMBRYOLOGY.

ovum does not, therefore, require consideration here ; on the other
hand, some older observations may be noticed, such as those of
Eeichert, Wharton Jones, and Breuss. The ovum of Reichert
especially has played and is still playing, though improperly, an
important role in human embryology.

Reichert' found the ovum in the uterus of a suicide and estimated its age
at twelve to thirteen or thirteen to fourteen days. It was completely enclosed
by the mucous membrane of the uterus. On the side of the capsule which was
turned towards the uterus there was a transparent area measuring 3 mm., which
Reichert termed the capsule sear, believing that at the sides of it the mucous
membrane of the uterus had grown up to surround the ovum. The ovum itself
was a lenticular vesicle, whose diameters were 5.5 and 3.3 mm. The surface of
the vesicle which was turned towards the uterus, the basal surface, was almost
flat, that turned toward the lumen of the uterus somewhat curved. The marginal
zone was richly furnished with small villi, the largest of which were 0.2 mm. in
length and were already partly provided with lateral branches. From the margin
small villi, diminishing in size, extended for some distance upon the surface of
the vesicle turned toward the uterus wall (the basal surface of Reichert) ; but at
the centre of the surface an area of about 2.5 mm. diameter remained free from
them. In the centre of this free area Reichert described a dull circular spot.
The surface of the ovum turned toward the lumen of the uterus was free from
villi. The statements that Reichert makes concerning the finer structure of the
ovum are in part insufficient and in part quite erroneous. Thus the wall of the
ovum could not have been, as he supposed, purely epithelial, nor the villi hollow
epithelial structures, but the wall must have been formed of mesodermal tissue with
an epithelial covering and the axes of the villi occupied by mesodermal tissue.
Reichert, indeed, perceived this mesodermal tissue, but regarded it as coagulated
material. Also what he says concerning the ingrowth of the \illi into the uterine
glands is undoubtedly incorrect. As regards the structure of the dull spot on
the uterine surface of the ovum, he supposed that it was formed by a layer of
small, finely granular, nucleated, polyhedral cells, situated within the epithelial
wall. It was taken for the embryonic anlage, and His has estimated the diameter
of this "embryonic spot" as 1.6 mm. That this spot really represents the un-
injured embryonic anlage is improbable, and KoUmann's statement in his " Hand-
atlas der Entwicklungsgeschichte des Menschen" (1907) — "From what we know
from the mammals this spot would now be regarded as the embryonic shield "
— is, as will be shown later, absolutely disproved. A definite opinion cannot be
given on account of the insufficiency of Reichert's description; nevertheless, I
regard as well founded the conclusion of Spee, that Reichert had destroyed the
actual embryonic structure during his preparation of the ovum and that in its
d^ree of development it would have occupied a place between the oviun of
Peters, to be described in detail later, and the Van Herff ovum of Spee. Probably
Reichert had casually obsen^ed the embrj'o; it may have been the spherical body
on the basal wall which he mentions on p. 26.

Another ovum which deserves mention is that described by Wharton Jones'
in 1837; it was of the size of a pea. The fisrure drawn from the preparation in
alcohol shows a diameter of 6.2 X 4.7 mm. The surface turned toward the lumen

* Reichert : Beschreibung einer f riihzeitigen menschlichen Frucht im blaschen-
formijsren Bildungszustande, etc., Abh. Kgl. Akad. d. Wiss., Berlin, 1873.

' Thomas Wharton Jones : On the First Changes in the Ova of the Mammi-
fera in Consequence of Impregnation and on the Mode of Origin of the Chorion,
Philosoph. Transact. Royal Soc. London, 1837, p. 2.

OVA AND VERY YOUNG EMBRYOS. 23

of the uterus was free from villi Imbedded in the cavity of the ovum was a
spherical body, with a diameter of 1,5 mm., which His, probably correctly, identified
as the embryonic structure, that is to say, the actual embryonic anlage together
with the amnion, yolk sack, and belly stalk. His assumes that this embryonic
structure may have been artificially displaced.

Next comes an ovimi described by Breuss * in 1877. It was expelled together
with the entire lining of the uterus. The wall of the ovum, which had a diameter
of 5 mm., consisted of two layers, the outer of which was epithelial and the
inner formed of connective tissue. The villi were for the most part unbranched
and were about 1 mm. in length and 0.07 mm. in diameter; they left free a
roundish area 2 mm. in diameter. Vessels could not be distinguished in their
interior. A projection which occurred in the interior of the ovum, consisting of
nucleated cells and having a length of 1 mm. and a diameter of 0.5 mm., may
have been the embiyonic structure. If it is assumed that the ovum was normal,
we must suppose that Breuss overlooked the amniotic cavity and the cavity of
the yolk sack, a supposition which I regard as possible.

Mention may also be made of two other ova, described by Allen Thomson.*
In one of these the embryonic structure must be regarded either as pathological or
as not corresponding to the degree of development of the oviun. Thomson estimates
the age of the smaller of the two ova at twelve to thirteen days. It had a
diameter of 6.6 mm., was everywhere surrounded with villi, and was almost com-
pletely filled by a vesicle which was apparently the yolk sack. Upon the yolk sack
was an embryo 2.2 mm. long and with both its cranial and caudal ends separated
from the sack. Thomson makes no mention of an amnion, but we may suppose
that it was present and covered the embryo on the surface opposite the yolk
sack; and a belly stalk must also have been present, since Thomson states that the
embryo was attached by its dorsal surface to the external egg membrane, that is
to say, to the chorion.

Although the ovum is larger than that of His, to be described below, the
second observation of Thomson may be recorded here; it concerns an ovum
measuring 13.2 mm. in diameter, whose age was estimated at fifteen days. It was
oval in shape and was evenly surrounded with villi. In the interior was a large
cavity filled with fluid; and at one spot was the embryo, closely attached to the
chorion and with a yolk sack and the remains of the amnion. The embryo had
a length of 2.2 mm. and its cranial and caudal ends projected somewhat beyond
the yolk sack. Viewed from the surface turned toward the chorion, it showed
distinctly the medullary folds, which manifested a tendency to fuse at the middle
of their length; ventrally was the heart. The diameter of the yolk sack was also
2.2 mm.; nothing is said concerning an amnion, but a lobe which is shown in
Thomson's figure at the head end of the embryo is apparently the remains of
an amnion that had been destroyed during the preparation of the embryo. It is
interesting to note that Kolliker* in 1879 regarded this second ovum described by
Thomson as not quite normal on account of the large space which separated the
embryo and yolk sack on the one side from the inner surface of the chorion on
the other. We now know that this is the normal condition in embryos of this
stage; and it is rather the smaller of Thomson's ova, which Kolliker was inclined
to regard as normal, that shows abnormal conditions, since the yolk sack never
fills the chorion so completely either in human or mammalian ova of this stage.

In all the ova so far mentioned a correct identification of the embryo, the

* K. Breuss : Ueber ein menschliches Ei aus der zweiten Woche der Graviditat,
Wiener med. Wochenschrift, 1877, pp. 502-504.

•Allen Thomson: Edinburgh Med. and Surg. Journal, vol. ii, 1839; and
Froriep's Neue Notizen, vol. xiii, 1840.

•A. Kolliker: Entwicklungsgeschichte des Menschen, 1879.

24 HUMAN EMBRYOLOGY.

yolk sack, amnion, belly stalk, and chorion is possible only in the two described
by Thomson, which contained embryos already rather well developed; and even
in these the identifications were only general ones, as may be seen from Kolliker*s
conmients upon the ova. He regarded, on the basis of the information available
at that time, the normal ovum as abnormal and the abnormal one as normal,
and the same conclusion was reached by Ecker, another distinguished embryologist
of the time. A definite idea of the relations of the amnion and the belly stalk
was also impossible for KoUiker. A correct interpretation of the discoveries
mentioned could not be given at the time of their publication and, indeed, in
part, not for some time after. The investigators who sought such interpretations
were led from the right path, and Reichert's ovum, as I have stated, gave rise
to many false ideas, even up to recent times. Consequently, as Elze and I^
have already pointed out in our "Normentafel zur Entwicklungsgeschichte des
Menschen," an observation by His* marks an important advance. The ovum in
question (No. XLIV [Bff.] of His's collection) had a greater diameter of 8
mm. and, at right angles to this, a diameter of 7 mm.; it was somewhat flattened
and at one point the villi were somewhat fewer than elsewhere. " On opening it
there was found, on one wall, a small body measuring 1.4 mm. in its longest
diameter and consisting of an ellipsoidal opaque body with a transparent vesicle
attached to it. The opaque body, which seemed from partial foldings of its
surface to be hollow, had a greater diameter of 0.85 mm. and a diameter at right
angles to this of 0.6 mm. The transparent vesicle surrounded by its border one
end of the ellipsoid. The connection with the chorion was by means of a short
stalk, which stood in relation to both the vesicle and the ellipsoid." " I regard,"
His says in another place, " the more solid body as the umbilical vesicle and the
transparent part as the amnion, and conclude from this that the embryonic
anlage, so far as it is present, lies at the boundary between the two. With this
idea the manner in which the structure is attached to the chorion agrees. That
is to say, the place of attachment lies on the boundary between the vesicle and
the opaque body." His^s interpretation, we can say to-day with all certainty,
is in agreement with the actual facts, and His was the first to give a perfectly
correct interpretation of a human ovum of this stage. He further reported con-
cerning this oviun that to the lower pole of the yolk sack there were attached
threads of that looser tissue "which traverses the cavity of the ovum, one of
these threads being especially distinguished by its tougher consistency and its
opacity."

Later observations of young human embryos, carried out with the methods
of modem technic, and especially with the aid of well stained and perfect series
of sections, have, as has been already stated, confirmed His's views and have
led to further, partly unexpected, results. It was the observations of Graf
Spec, especially, that opened the way, and, later, H. Peters rendered great sendee;
but for the sake of continuity the ova in question will not be described in the
order in which they were discovered, but according to their degree of development.
Consequently I shall begin with the ovum described by Bryce and Teacher.*

The ovum was obtained from an abortion, and although the presen'ation
of the embryo proper is not perfect yet it is of the greatest importance; Fig. 10
shows the ovum as it lay in the uterine mucous membrane, according to a diagram
by Bryce. With the exception of a small area it is completely surrounded by

* Franz Keibel and Curt Elze : Normentafel zur Entwicklungsgeschichte des
Menschen, Jena, 1908.

•W. His: Anatomie menschlicher Embryonen, Leipzig, 1882, part ii, pp. 32
and 87 et seq. See also Mall, Joum. of Morph., vol. xix, p. 151.

•Bryce, Teacher, and Kerr: Contributions to the Study of the Early Develop-
ment and Imbedding of the Human Ovum, Glasgow, 1908.

OVA AND VERY TOUNO EMBETOS. 25

decidua, and the opening in the decidua (capsularis) is closed l^ coa^ated
fibrin containing leucocytes. A large opening with fungoid tissue (the closing
coagulum of Bonnet) is wanting.

The ovum, surrounded with blood, lies in a relativelj laige chamber, with
whose walls it is not united; the maternal and fetal tissues are quite separate.
The uinermost layer of the decidua, which forms the capsule of the ovum, is in
an advanced stage of coagulation necrosis and, together with some deposits of
fibrin, fonns around the ovum a capsule of dead tissue, which is interrupted only
at one or two places, where blood-vessels open into the egg chamber, and at
one where a hemorrhage has broken through into it.

FiQ. 10.— Diacram of IhE ovum of Tocher and Bryoe. after Brv«. P.t.. poiot of entnooe; cvl-.
oytotrophoblut; jA., pLaBmodilrophoblast; nj.. necrolic d«ddua tone; Qi.. aLanda; tap,, eapillaries; jA'-,
vBcuoli*ed pltwmodiB nhicb mre penetntloc cupillaries. The cavity of the ovum is completely filled witli
meioblaflt» And in this ih« medullo-BiDniotia and «ntodermic (iatettine-yalk aaclc) vesicles are jrnbedded,

tiona. eM., 1908, p. «, Fig. VII.>

The wall of the ovum consists of an inner layer (the cytotropboblast, the
layer of Langhans's cells), whose cells are poorly separated from one another
and externally pass over into a very irregnilarly arranged plasmoditropboblast ; tbis
has a distinctly plasmodial character and forms a loose network, whose spaces
are filled with maternal blood. The cytotropboblast is nowhere continued into
the plasmoditropboblBBtic trabecule.

The cavity of the ovum is occupied hj a delicate tissue which has the
characters of mesenchyme. This primitive mesoblast shows no traces of a
splitting into a parietal and a visceral layer; there is, accordingly, no ccelom.
Alao, projections of the mesoblast toward the cytotropboblast (mesodermic villi)
are not yet present.

The embryonic structures (the embryo together with the amnion and yolk
sack) are represented by two vesicles which have an excentric position, and are
completely separated from the cytotrophoblaat by the mesenchymstous tissue.

26

HUMAN EMBRYOLOGY.

The cavity of the larger vesicle is supposed to be the amniotic cavity and that
of the smaller the cavity of the yolk sack. The cells which enclose the amniotic
cavity are cubical and those enclosing the yolk sack are flattened, but in neither
vesicle do they show individual differentiation.

The egg-chamber is oval in form, the longest axis, lying parallel to the
surface of the uterus, measuring 1.95 mm.; perpendicular to this and also
parallel to the uterine surface the lumen of the egg-capsule measures 1.1 mm.
and its depth (perpendicular to the surface of the uterus) is 0.95 mm. Since
the wall of the ovum itself is folded the measurements of the cavity can be
stated only approximately as 0.77 and 0.63 mm. The relative sizes of the
amniotic cavity and of the yolk sack may be perceived from Fig. 10 ; unfortunately
these structures were not intact.

The estimate of the age of the ovum made by Teacher and Bryce is very
interesting and important, since it is based on exact data concerning the men-
struation and the cohabitations. They estimate the age at thirteen to fourteen
days, the ovum haWng been expelled sixteen and one-half days after the fertilizuig
coitus. The cause of the abortion is supposed to have been a later coitus. If
this estimate be correct the other ova to be described later on are all older than
has hitherto been supposed. The table given by Bryce and Teacher may be
reproduced here.

TABLE I. (From Bryce and Teacher.)

Chronological table of twelve well-described early pregnancies. Fertilization is assumed to be
effected about 24 hours after insemination, and 24 to 48 hours are allowed for the completion of abortion.
The leading data are supplied by the histories of Nos. 1, 4, 6, 8, 9, 10; and the position of the remainder
is adjusted according to their dimensions and state of development. The ages according to the conven-
tion of His are shown in the colunm headed, " Days elapsed from omitted period."

B

Author.

1, Teacheb-Bryce. . 1.95x0.95x1.10

Dimensions in millimetres.

Orum.

External.

2 Peters
8' Juno...

2.4x1.8

Merttens
Beneke ..

6i Von Spee (Von
Herff)

Leopold

8' Reichert

9 Rossi Doria

10 Aternod

4.0x3.0

6.0 X 4.5

6.0x6.5

11 Frassi

12, VoN Spf.e (Glae-
vecke)

9.0x8.0

10x8.2x6.0

13x5.0

Internal.

0.77x0.63x0.52

1.6x0.8x0.9
2.5x2.2x1.0

3.0x2.0
4.2x2.2x1.2

4.0

4.0x3.7

6.5x3.3
6.0x6.0

6.0x4.8x3.6
9.4x3.2

10x8.5x6.5

Days elapsed

Elmbryo.

e^ From beginning
* of last period.

o
34

about
0.15

0.16

30

• •

• • • •

32

B •

• • • •

21

16

like 6
but

25

20

young' r
0.37

40

• •

• • • •

15

10

> • • ■

42

■ •

« B • •

28

24

1.3

34

■ ■

1.17

42

• •

1.54

40

•9

S-5

u

Age in
days.

10

Remsrks.
How obtained.

13-14 Abortion 16i days after
cohabitation.

12

14-15
14^-15^

14i-15i
16-17

17-18

17-18

17-18
18-19
18-19

14 ; 18-19

I

I

12 1 19-20

14

Suicide. Autopsy.

Periods every 5-6
weeks. Curetting on
account of leucor-
rhoea.

Curetting.

Curetting.

Abortion two days
after b^^inning of in-
fluenza.

Hysterectomy: carci-
noma of cervix. Men-
struation during preg-
nancy (?) .

Sudden death. Au-
topsy.

Abortion with sudden
beginning and three
days' retention.

A single cohabitation
21 days before abor-
tion.

Hysterectomy ; metri-
tis chronica.

Recent abortion.

OVA AND VERY YOUNG EMBRYOS.

27

TABLE II. (From Bryce and Teacher.)

Showing the relation of the dates of fertilisation and of imbedding to the menstrual cycle,
calculated from the data given in Table I. The higher figure in the age column is arbitrarily chosen in
each instance, and allowance is made for the special circumstances of each case.

Fertilization.

Dajrs of menstrual period.

Imbedding.

Merttens . . .
Roeei Doria.
Beneke

1

2

8

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

Von Spee (Von Herff) 21

I 22

Frassi 23

24
25
26
27
28

£temod

Peters
Jung .

Von Spee (Glaevecke)

. . Merttens
Rossi Doria
Beneke

Teacher-Bryce and Reichert
Leopold

, £temod

Peters

Jung

Von Spee (Glaevecke)

Von Spee (Von Herff)

Days of succeeding menstrual period.

» Frassi

Teacher-Bryce and Reichert
'. Leopold

We now come to the ovum described by Hubert Peters"; it was obtained
at the autopsy of a woman who had poisoned herself with caustic potash.
Death had occurred within three hours after the taking? of the poison and the
autopsy was performed on the same day, a few hours after death. The ovum, to-
gether with the entire egg capsule, fixed by Prosector Kretz in Muller's fluid and
hardened in alcohol, was successfully stained and microtomized by Hochstetter;
it found in Peters an exceedingly careful observer. The uterus, from which the
ovum was taken, was the size of a goose's egg^ and thick-walled, and felt some-
what more doughy and softer than a normal utenis. " The decidua of the corpus
uteri was traversed by numerous furrows which crossed one another at various
angles and occasionally formed grooves, so that the mucous membrane between

10

Hubert Peters: Ueber die Einbettung des menschlichen Eies und das
friiheste bisher bekannte menschlichen Placentationsstadium, Leipzig und Wien,
1899.

28 HUMAN EMBRYOLOGY.

these bounding furrows formed root-like or occasionally rounded projections
toward the uterine lumen. In the middle of the posterior wall Prosector Kretz
noticed a small area which was of the size of a hemp seed, which was somewhat
paler but not prominent''; it contained the ovum. This was ellipsoidal in form,
its diameters being 1.6 X ^-8 X ^-9 nam., these measurements, however, being of
the cavity of the egg capsule. The part of the decidua in which the ovum lay
presented, as the study of the sections showed, a slight, rounded elevation toward
the cavity of the uterus. " While the decidua stretched as a very thin sheet, in
the form of a capsulaxis, over the lateral portions of the ovum, the summit of
the ovum was quite free from maternal tissue and projected freely into the
lumen of the uterus by means of a blood-granulation mass which rested upon it " ;
this mass Peters terms the fungoid tissue (Gewebspilz). If the interpretation
which Peters gives of the fungoid tissue is correct and it is not a post-mortem
phenomenon or a result of the poisoning, we have for the first time a human
ovum that is not yet quite covered by a capsularis. Later Spee {Verh. Anat,
Ges., 1902 (discussion of Marchand's paper) ; compare Schwalbe's Jahresber,,
n. F., vol. viii. No. 2, p. 298) stated that occasionally young ova were to be
found in which the egg capsule had an opening toward the uterus at the place
where the scar tissue occurred, and at the corresponding place the ovum of
Bryc« and Teacher showed, as has been mentioned, only a small opening and no
well-marked fungoid tissue. Upon the mesoblast layer of the ovum, which shows
indications of the first few and as yet but slightly developed \'illi, follows a
layer of epithelial cells, which reaches in places a thickness of more than 0.5 mm.
and is traversed in a honeycomb manner by smaller and larger blood lacun®,
but still remaining continuous at the periphery. Peters interprets this rightly,
as I believe, as an " ectoblast shell " and names it the trophoblast, adopting the
term which Hubrecht had proposed as a result of his observations on the hedgehog.
Its further significance will be fully considered in the chapter on placentation
and it will there also be compared with the corresponding structures of other
mammals (cheiroptera) and with what is found in older human ova (Kastschenko,
Merttens, Von Herff). As in the ovum of Bryce and Teacher differentiation of
the cells of the trophoblast investment was evident, and the cytotrophoblast
(Langhans's cells) and the spongiotrophoblast were distinguishable."

The embryonic anlage in this remarkable ovum was extraordinarily small,
the embryo measuring, as estimated from the sections, 190 fi in length. I quote,
as Peters has done, the description which Graf Spee has given of the cavity
of the ovum. " The entire cavity of the ovum enclosed by the chorionic ectoblast
[trophoblast shell, cytotrophoblast, and spongiotrophoblast] is filled up to the
cavities of the embryonic anlage with mesoblast. This latter is very irregular
as regards its possession of mesoderm cells. These are more numerous in the
mesoderm layer resting upon the chorion, this consisting of two or at the most
four cell-layers, presenting a greater thickness only in the region where the
embryonic anlage occurs." Exception must be made of those places where there
occur the mesodermic rudiments of the villi, already mentioned. " The more
central portions of the egg cavity are very poor in cellular elements. Only
scattered tracts of spindle-shaped mesoderm cells traverse it. In the intervals
there is a feebly staining fibrogranular mass which occupies most of the cavity.
The cellular tracts frequently unite with the mesoderm enclosing the embryonic
anlage and with that of the opposite wall of the ovum." Spee has found
similar cords in all younger human ova.

" Those portions of the trophoblast which come into relation with the
tissues of the uterine wall and take an active part in the implantation of the
ovum and in the excavation of the egg chamber have been termed trophoderm
by Minot (Charles S. Minot: The Implantation of the Human Ovum in the
Uterus, Trans. Americ. Gynaecol. Soc., 1904).

OVA AND VERY YOUNG EMBRYOS. 29

" The embryonic anlage (cut obliquely in the preparations) shows two
very small epithelial cavities (amnion and yolk sack), completely surrounded
by mesoderm and contained within a thickening of the chorionic mesoblast. The
amniotic cavity is completely closed. Its wall is differentiated into a very thin
amniotic membrane, lying nearer the surface of the ovum, and a plate con-
sisting of high cylindrical cells, the germinal disc (germinal shield, embryonic
shield). Between these and the wall of the yolk sack, composed of entoderm
cells occasionally diflficult to recognize, a layer of mesoderm is interposed. At
one (the cranial) end (section 49 [44, 43f]) the cellular portion of the mesoblast
does not appear to reach the median line. It lies on the yolk sack and is
separated from the ectodermal territory by a * membrana prima.' This mem-
brana prima (Hensen) always develops as a fine contour at the boundary between
the ectoblast and mesoblast. It extends across the middle line in the preparations.
. . . The series of sections clearly reveals the relations of most portions of
the embryonic anlage. One end of the series only presents difficulties in the
way of observation, partly on account of the unfavorable plane of the sections
and partly, perhaps, on account of some complications in this region; for in-
stance, it is impossible to determine the continuity of the ectoblast and mesoblast
in some sections, and the condition of the yolk sack cannot be made out in this
region." Spee considers this to be the caudal end. " An isolated cord con-
necting the embryonic structures with the chorion cannot be said to exist, since
almost the entire embryonic anlage seems to be imbedded in a thickening of
the chorionic mesoderm. Whether the first small rudiment of an entoblastic
diverticulum (the allantoic duct) has begun to bud out and is represented by a
ring of epithelium-like cells arranged around a lumen, is altogether uncertain."
Grosser figures a section through the ovum in situ (see Fig. 96, from Peters's
figure) in the chapter on the development of the egg membranes and the
placenta. I have reconstructed the embryonic structures from plates left by
Selenka and found neither an allantoic nor an amniotic duct. The surface of
the yolk sack appeared warty, as if the blood and vessels were beginning to
form upon it; naturally, the wax plates and the model give no definite informa-
tion on this point.

The ovum which Graf Spee has described, unfortunately only briefly {Verh.
deutsch. Ges, Gynak., 1905, pp. 421-423; compare Schwalbe's Jahresb., n. F., vol. xi.
No. 2, p. 241), comes nearest to that of Peters. In a woman poisoned by oxalic
acid one of the swollen areas of the mucous membrane on the ventral wall of
the uterus immediately in front of the opening of the right tube was markedly
prominent and its depressed summit showed a distinctive coloration. In it was
found, in an egg capsule of 1.5 X 2.5 mm. diameter, an ovum poorly provided
with villi and with a very small embryonic anlage that was surrounded by a
quantity of blood. The summit of the egg capsule showed an implantation open-
ing, which was 0.8 mm. in diameter and covered by a very flat blood-dot; in its
neighborhood the villi were more numerous than elsewhere. Very near is also
an ovum studied quite recently by Ph. Jung"; it was obtained from an abrasio
mucossB. The preparation is splendidly preserved and apparently normal. Jung
confirms in general the observations of Peters and Spee; comparatively little
attention was devoted to the embryonic structures, and it is very desirable that
these should be thoroughly studied. The cavity of the ovum measured 2.5 X 2.2 mm.

The Von Herff ovum described by Graf Spee" takes its place in the
series here. It was expelled after a menopause of five weeks on the second

"Ph. Jung: Beitrage zur friihesten Eieinbettung beim menschlichen Weibe,
with 20 figs, on 7 plates, Berlin, 1908.

" Graf von Spee : Neue Beobaehtungen iiber sehr f riihe Entwicklungsstuf en
des menschlichen Eies, Arch. f. Anat. u. Physiol., Anat. Abt., 1896.

30 HUMAN EMBRYOLOGY.

day after a severe attack of influenza, probably as a result of the illness,
and was apparently normal; it was throughout richly supplied with villi. Spee's
remark that the diameters of the egg capsule, which he believes must have been
really about 7 and 5i mm., were actually greater than these, is based upon the
fact that the capsule was strongly distended with blood. Since, however, the
periphery of the ovum must have reached the maternal tissues such a condition
cannot be regarded as normal, but must have arisen shortly before or during
the abortion. Spee estimates the diameter of the space within the chorion at
barely 4 mm. The thickness of the chorion was 0.9 mm.; the villi measured
0.16-0.18 mm. at the base and were separated from each other by intervals of
0.2-0.78 mm. where the distance could be determined. The villi were covered by
a double layer of cells, the Langhaus layer and the syncytium, the latter, although
not so well developed as in later stages, being nevertheless quite distinct. Both
layers are regarded as differentiations of the ectoblastic trophoblast shell, as
cytotrophoblast (the Langhans layer) and spongioblast (the syncytium).

The embryonic structure had the form of an elongated thick papilla,
attached at only one of its extremities to the chorion and elsewhere projecting
quite freely into the interior of the cavity of the ovum (that is to say, into
the periembryonic mesoderm space, the exocoelom of Selenka). Its long axis cuts
the chorion at a very acute angle. A superficial furrow marks off on the papilla
two elliptical portions. The larger of these forms the free pole of the papilla
and proved to be the relatively very large yolk sack; the smaller one contains,
on the surface which lies close to the chorion, a completely closed cavity, which
was the amniotic cavity with its ectoblastic lining, but for the rest it is a
compact cord composed of mesoderm, which extends from the mesoblastic cover-
ing of the yolk sack to the chorion, surrounding almost three-fourths of the
amnion, so that this structure seems to be sunken into it. This part is the actual
belly stalk and the sole connection with the chorion. In it there was an allantoic
duct extending from the yolk sack. The portion of the ectoblastic lining of the
medullo-amniotic cavity that rests on the yolk sack consisted of cylindrical cells
and formed a thick plate, evidently the embryonic shield (the germinal disk).
The plane of the embnonic shield is somewhat peqiendieular, that is to say,
radial, to the surface of the chonon, the head end being nearest it. In the
model the embryonic shield presents an oval outline and a median furrow lying
between lateral portions which are convex dorsally and are somewhat unequal in
size in the transverse direction. At the same time the dorsal surface of the
shield is adapted to the form of the amniotic cavity and is, on the whole, concave.
Spee gives the following measurements:

" Direct measurements of the embrj-onic papilla : Longest diameter, 1.84 mm. ;
diameter through the constricted portion, 0.475 mm. Almost perpendicular to
these the longest diameter of the yolk sack is 1.054 mm. The amnion together with
the belly stalk measures 0.76 mm. ; the greatest length of the two latter structures
is 0.76 mm.; the greatest breadth of the yolk sack, 1.083 mm.; its thickness about
the same.

" Measurements taken on the model (divided by 100 and so reduced to
the actual size): Length of the germinal disk, 0.37 mm.; its breadth, 0.23 mm.
(this is the ectoblast plate of the germinal disk) ; height of the amniotic cavity,
up to 0.34 mm.; thicknef^s of the belly stalk together with the amnion, 0.62 mm.;
length of the allantoic duct, 0.35 mm."

An amniotic duct or cord was not present. The entire anlage of the germinal
disk (embryonic shield) was apparently, ac<*ording to Spee, only a portion of
the primitive streak region, notwithstanding that the typical fusion of the ectoblast
and mesoblast could not be recognized in the sections, probably as a result of
the preparation. No trace could be found of a differentiation of the medullary
plates or of the chorda. " The primitive streak resrion extends right up to
the cranial end of the germinal disk" (the embrj'onic shield).

OVA AND VERY YOUNG EMBRYOS. 31

The walls of the yolk sack seem to have advanced further in development
than any other part of the embryonic anlage. The lining of its cavity is through-
out single-layered and formed by cubical cells. Its mesoblastic covering forms
irregular elevations and knobs, which project like small papillaB, especially over
the pole that is turned away from the embryonic shield. In each papilla a
blood island was interposed between the mesoblast and entoblast and produced a
bulging of the mesoblast, but very little irr^rdarity of the entoblast. The
formation of blood islands ceased at a much less distance from the embryonic
shield in this ovum than in Von Spec's Glaevecke embryo, to be described later.
The youngest stages of the blood islands lay nearest the embryonic shield; the
oldest, at the distal pole of the yolk sack.

Near to this Von Herff ovum — indeed, according to the opinion of its
finder somewhat younger — is that which Beneke" found in a curetting done for
therapeutic reasons. The curetting was made March 30, 1903, the last menstruation
having lasted from March 5 to 10. No cohabitation had occurred after March 22.
The cavity of this ovum was 3.8 mm. long, 2.2 mm. broad, and 1.2 mm. highj
and the embryo itself had a length of 1.74 mm.," its greatest thickness in the
dorsoventral diameter being 0.6 mm. The meduUo-amniotic cavity was elongated
caudally in a fusiform manner and was connected with the chorionic ectoblast by
a cord of epithelial cells. It is stated that a typical medullary epithelium was
already present in the anterior part of the germinal disk, and mention is made
of a head process and of a chorda-like mass of cells. A neurenteric canal was
present, but an allantoic duct was " not distinct." Although the statements in
the brief description are not always as clear as could be desired, yet it seems to
me, from the presence of a canalis neurentericus, of an amniotic duct or cord,
and of an anlage of the medulla at the anterior end, that the embryo is more
developed than that of the Herff ovum described by Spec.

A thorough study of the ovum is expected and when its results appear more
definite conclusions will be possible; a thorough description may also make clear
the meaning of certain peculiar structures that have been taken for blood-vessels,
but which I shall not discuss here.

The embryonic anlage of an ovum described by Carlo Giacomini ** was
probably in about the same stage of development as the Spee embryo Von Herff;
but on account of its poor preservation it would not have deserved mention
here were it not that Giacomini states that it was expelled eleven days after a
single cohabitation, so that its age may be estimated at nine or ten days, an
estimate that does not agree with the conclusions of Bryce and Teacher that have
been thoroughly discussed and reproduced above. The occurrence may also be
noted of a small duct that opened on the surface of the chorion near the point
of fixation of the embryonic structures and has been identified by Marchand "
as the remains of an amniotic duct. A young ovum described by Mall '*
may also be mentioned here, although since it possessed a well-developed

"Beneke: Ein sehr junges menschliches Ei (Ost.-Westpreuss. Gesellsch. f.
Gynakol.), Deutsche med. Wochenschrift, Jahrg. xxx, 1904; and Mitteilungen
und Demonstrationen mit dem Universalprojektionsapparat iiber ein sehr junges
menschliches Ei, Marburger Sb., 1908, pp. 29-38.
Surely a misprint.

Carlo Giacomini: Un novo humano di 11 giorni, Giomale della Reale
Academia di Medicina di Torino, vol. iii, anno 60, Fasc. 10-11, Torino, 1897.

"F. Marchand: Beobachtungen an jungen menschlichen Eiem, Anat. Hefte,
vol. xxi, 1903.

"Franklin P. Mall: A Contribution to the Study of the Pathology of
Early Human Embryos, Johns Hopkins Hospital Reports, Festschrift for Welch,
vol. ix, 1900. Also Joum. of Morph., vol. xix, p. 144, 1908.

u

16

32 HUMAN EMBRYOLOGY.

Allantoic duct, it may have been somewhat older. Its diameter favors this view.
Its long diameter was 10 mm. and its short one 7 mm., and, like the Reichert
ovwn, it had villi only around its greatest circumference, two areas being thus
bare. The villi were 0.5-0.7 mm. long and were branched. Mall now regards
the oMun, probably correctly, as being pathological.

A very interesting ovum, similar, but probably in a slightly older stage
of development, is described by Siegenbeek van Heukelom," who unfortunately
considers the embryonic structures only casually.

It was obtained from a woman who received some bums during an epileptic
attack and died six hours later. An autopsy was performed fourteen hours after
death. With the exception of the bums the body showed no noteworthy departures
from the normal. The entire uterus was placed in 3 per cent, formalin for some
<iays and was then washed and fixed in alcohol. Since the ovum was collapsed as
the result of a slight tear, accurate measurements could not be made; but Van
Heukelom estimates its meridian at about 16i mm., which would give a diameter
of 5.1 mm. The ovum was completely covered with villi; the insertion of thirty-
one of these could be counted in a meridional section, fifteen occurring on the
basal portion of the section (the portion nearest the uterine wall), twelve at the
opposite pole, and two on each side at the equator. The villi of the embryonic
pole were better developed than those of the opposite pole, and those at the
-equator were " especially heavy and thick." They varied greatly in length, some
being small and short, the majority 0.75 mm. long and those at the equator
as much as 1 mm. Some were little branched, others, especially the basal and
equatorial ones, had many offsets, and some divided into numerous branches. The
epithelial covering of the villi was composed of two layers; the outer showed no
cell limits, so that we have to deal again with the Langhans layer and the
syncytium, a cytotrophoblast and a spongiotrophoblast. All the large branches
of the villi were connected peripherally by means of epithelial trabeculaB (ectoblast
trabeculflB, cell columns) to form an epithelial shell (ectoblast or trophoblast shell)
provided with large and small spaces. This shell was often very thin, consisting
of only a single cell layer; at other times it was very thick and in its thicker
parts there were peculiar blood lacuna, resting directly upon the maternal com-
pacta. The remaining conditions resembled in essence those of the Von Herff
ovum of Spec. At the basal wall of the ovum was the embryonic papilla (the
embryonic structures) united to the chorion at a very acute angle by a stalk. A
distinct allantoic duct was present and the amniotic cavity was lower than in
the Von Herff ovum described by Spee. Only one of the sections through the
embryonic shield is figured, and this is reproduced here as Fig. 11. In it, in the
region of the primitive streak, a mass of cells is seen projecting beyond the
surface of the shield; Van Heukelom suggested that this might be Hensen's
node, a suggestion which I, as well as the author, would mark with a large note
of interrogation. Nothing is said of an amniotic duct.

Somewhat older again is the ovum that I** described in 1890; it contained
an embryonic shield with a well-developed primitive streak and was the first of
this stage to be described. The ovum was expelled in an abortion with the egg
capsule, which was lenticular in shape and measured 12 X ^i X 7 mm. ; it had a
scar measuring 2i mm. Like all human ova of this period it was easily separated
from the capsule, and measured SiX^iX^ mm. It had two areas free from
villi : a larger one, measuring 6i X ^f ^^n., at the pole opposite the embryonic
anlage, that is, the pole toward the lumen of the uterus; and a smaller one at

" Siegenbeek van Heukelom : Ueber die menschliche Plazentation, Arch, f .
Anat. u. Physiol., Anat. Abt., 1898.

* Franz Keibel : Ein sehr junges menschliches Ei, Arch, f . Anat u. Physiol.,
Anat. Abt., 1890.

OVA AND VERY YOUNG EMBRYOS. 33

the embryonic pole, situated exeentrically in front of the point of attachment of
the belly stalk and measuring 2 mm. in diameter. The tissue of the Reichert
scar showed neither glands nor blood-vessels, nor was it bounded by epithelium.
The structure of the chorion and villi was the same as in the Spee ovum Von
Herff, except that the syncytium was more strongly developed. The embryonic shield
was about 1 mm. long and showed in the sections a well-developed primitive streak.
The yolk sack liad a diameter of 1 mm. ajid showed numerous blood and blood-
vessel aniagen. The endotlielial walls of the blood-vessels were already clearly
distinguishable from the blood-corpuscles. There was an allantoic duct.

Fio. 11. — Section tfarouch the bEsal portion oF (ha ovum described by Sircenbeek van Heulfelom.
with the embryonic nruetunn (embryonic papillal. a, Intervilloiu span; b, villus; e. ectoblnirt man of
a villus not included in this section: d. outer, epithelial layer of chorion; e. inner, mesoblostio layer of
ghorioa (piuielal mesoblon); /, clot sjid granular deposiCe; (r, mesoblanic alalk; h. part of (he italic
with mooy cells; i. amnion; k. embryonic ihield in croes-KC(ion (eo(ablas(): 1, mesoblBS(; m. hypoblaK;
n. hypoblast of (he yolk sack; o, visceral layer of mesoblast; p, maternal blood. (After 8i<«enbeek
van Heukelom: Ar«h, f. Anatomie u. Pbyuol., Anat. Abt.. 1S68.)

The ova described by Merttens," by Leopold " in his Atlas, by Marchand and
by Rossi need be mentioned here only in so far as they present especially striking
peculiarities. Merttens had for study only four sections found accidentally in
the investigation of a uterine curetting. Leopold in his ovum obtained by opera-
tion and estimated by him, " with doubtful accuracy," according to Spee, to be
seven to eight days old — it was undoubtedly older — found no distinct embryonic

"J. Merttens: Beitrage zur normalen und patholog. Anat. der menschl.
Placenta, Zeitschr. f. Geburtsh. u. G>-nakol., vol. xxx, 1894, and vol. ixsi, 1895.
"0. I^opold: Uterus und Kind, Leipzig, 1897.

84

HUMAN EMBRYOLOGY.

papilla, either on account o£ unsatisfactory preservation, as Van Heukelom Eug-
gesta, or, as Spee believes, because the ovuni was abnormal. At all events the
ovum, whose diameter was 4 X 3-7 mm., need not be further considered here.
Couceming the ova described by Marchand (1898) I may remark briefly that
that author describes {Marburger 56., 1898, pp. 150-153), in an imperfectly
preserved o\-um of the size of a pea, at that portion of the surface of the
chorion where the remains of the embryonic anlage occurred, a funnel-like de-
pression of the surface of the
chorion which led into a canal
filled with syncytium; this he
interpreted as the remains of an
amniotic duct."

From two later publications
by Marchand (" Beobachtungen
an jungren menschlichen Eiem,''
Anat. Hefte, No. 67, vol. xxi,
1902, pp. 217-278; and " Einige
'* Beobachtungen an jungen mensch-

lichen Eiem," Verh. Anat. Ges.,
1902) it may be noted that
he found in one ovum " that the
intervillous space was not filled
with maternal blood, not with-
standing that the blood-vessels
of the neighboring portions of
the mucous membrane were es-
oessively engorged. The inter-
villous space seemed to be sepa-
rated from the cavity of the egg
chamber peripherally by strong
ectoblastic proliferations; blood-
vessels opening into the cavity
of the egg chamber could not bs
found. From this it would fol-
low that the blood must normally
enter the inter\'illous space only
at a later period of development;
a precocious entrance of the blood may, according to Marchand, lead to an abortion.
Also, according to Rossi Doria," who described an ovum of less than
9X8 mm. contained in a completely closed egg capsule, an actual circulation of

"In a later publication {Anat. Hefte, 1903, p. 223) he says: "We have
to do therefore with a narrow canal traversing the choritn, which from Its opening
at the surface is lined or, more properly, filled by a prolongation of the so-called
surface epithelium, and ends blindly a short distance below the inner surface,
just where the remains of the embryonic anlage occur." He ascribes the same
significance to a depression on the surface of the chorion of an ovum of 14 X 3 mm.
diameters, which was laterally compressed by a blood-clot.

"The ovum was obtained from the body of a woman who had died as the
result of a gunshot wound. It was studied in situ, but the ovum and egg capsule
were folded; the latter, according to Marchand, had a length of about 1.5 cm,
and a breadth and depth of about 5-6 mm. The entire ovum was covered with
branched villi. The embryo was completely disintegrated,

" Tullio Jiossi Doria : Ueber die Einbettung des menschliehen Eies, studiert
an einem kleinen Ei der zweiten Woche, Arch. f. Gynakol., 1905, vol. Issvi, pp.
433-505.

Fig. 12, A mnd B.— F«ucM of the embryonio ghield al
iba Fn«d ovam, from a model by £Ih. Ilie belly stalk,
loseiher irith the portioa oC the chorion lo which It is miached,
ii itKiwn to lh« risht; the yolk uck and tranion hAve been
removed, in A one ia Lookins down upon the shield; at about
its middle ia (he donsi opeaing of the cajwlis neurenlcricus,
to the left of this is the ihallaw meduUacy groove Qanked by

In the belly stalk It

. The plane of th

i: Arch.f.mikr, A

OVA AND VERY YOUNG EMBRYOS. 35

the blood does not take place at the beginning of the second week of develop-
ment, because at that time the maternal blood has not yet gained access to the
intervillous space; he regards the so-called prickle processes on the surface of
the syncytium as a deposit formed from degenerated blood-corpuscles and the
" scar " of the egg capsule as formed by regressive changes of the summit of
the reflexa. Nothing is stated concerning the embryonic anlage, and the entire
ovum was apparently little favorable for the settlement of important questions.
We may now consider an ovum obtained by operation and studied by Frassi **
under my direction. The entire uterus, removed per vaginam, was at once placed
in a warm 5 per cent, solution of formalin; it remained there forty-eight hours
and was then washed for twelve hours and finally passed through alcohols of
gradually increasing strength. Only then was it opened, cut into portions, and
these imbedded in celloidin, in which condition it came into the hands of Frassi.
The ovum, together with the portion of the uterus that contained it, was cut into
serial sections. The ovum and embryonic structures were undoubtedly normal.

Fio. 13. — Section of tbe embryonic anlage of the Frassi ovum, taken 30 ^ cranial to the dorsal open-
ing of the nenrenteric canal; the head process is cut obliquely and the ventral opening of the neurenteric
canal practicaUy tangentially. X 50. (From Frassi: Arch. f. mikr. Anat., vol. Ixxi, 1908.)

The diameter of the egg capsule parallel to the surface of the uterine lumen,
in the plane of the sections, was 13 mm., perp)endicular to this surface it was
5 mm. at the middle of the ovum; the corresponding diameters of the cavity of
the ovum were 9.4 and 3.2 mm. A scar could not be detected in the decidua
capsularis. The ovum was completely covered with villi, which were especially
developed in the equatorial zone; their length varied between 0.5 and 1.9 mm.
Both blood-vessels and glands opened into the intervillous space, but with regard
to the latter it could be perceived that they had been laterally eroded, so that
their communication with the space was secondary. It is remarkable that practically
no blood was contained in the intervillous space, notwithstanding that blood-
vessels opened into it; it must be that the blood had completely escaped during
the operation. The Langhans layer, syncytium, and cell columns were present;
and of these the Langhans layer and the cell columns may be regarded as cyto-

" L. Frassi : Ueber ein junges menschliches Ei in situ, Arch, f . mikr. Anat.,
vol. Ixx, 1907; and Weitere Ergebnisse des Studiums eines jungen menschlichen
Eies in situ, ibid., vol. Ixxi, 1908.

36

HUMAN EMBRYOLOGY.

trophoblast and the syncytium as spongiotropboblast. The embryonic shield was
cut somewhat obliquely; it showed the anlage of a well-developed primitive streak,
at the anterior end of which was a neurenteric canal and at the posterior end
the cloacal membrane. The section shown in Fig. 14 passed directly through the
neurenteric canal. In front of the primitive streak is a flat medullary groove,
bounded by still indistinct medullary folds. Anlagen of blood and blood-vessels
occurred on the yolk sack. Anlagen of blood-vessels could be seen with certainty
in the mesoderm of the chorion only in the nei^borhood of the insertion of the

-Ch.

Fio. 14. — Section of the embryonic anlage of the Frassi ovum through the dorsal opening of the
neurenteric canal. At the opposite pole of the yolk sack are anlagen of blood and of blood-vessels, and
in addition a small cyst lined with coelomic epithelium; it is shown more highly enlarged in Fig. 14a.
Over the amnion is a portion of the chorion {Ch.) with a cut origin of a villus. X 50. (From Frassi: Arch,
f. mikr. Anat., vol. Uxi, 1908.)

belly stalk; none could be detected in the mesodermal axes of the villi. Models
were made of the embryonic structures as well as of the embryonic shield, but
only those of the shield need be figured here, together with some of the sections.

The measurements, made on the model, were:

1. Length of the embryonic shield 1.17 mm.

2. Breadth of the embryonic shield 0.6 mm.

3. Length of the primitive streak 0.5 mm.

4. Diameter of the yolk sack,

a. Greatest 1.9 mm.

6. Least 0.9 mm.

The embryonic structures were attached to the inner surface of the chorion
by a typical belly stalk, in which vessels could be made out.

We come now to the ovum Gle (Glaevecke), the careful study of which
by Graf Spee has done so much to advance our knowledge of human embryology.
It was an aborted ovum that was expelled, together with the entire uterine mucous

OVA AND VERY YOUNG EMBRYOS.

37

membrane, five weeks after the cessation of the menses. The diameter of the egg
capsule parallel to the surface of the decidua was 10 X H mm., and perpendicular
to this, the thickness of the decidua basalis being included, 7.2 mm. The ovum
was everywhere, but not very thickly, covered with villi. It was somewhat oval,

. D.B

Tia, 14it.— Th« lower pole of the yolk h
ovum leproduoed in Fig. 14 with the Ullage o
epithelium of yolk uck; C. E.. nclomie epitbeli
Fniii : Areb. f. mlkt. Aoat.. vol. Ixii, IMS.)

le (mbryoDie structurea of the Fnta

m; E.d.C epilbaliuDi of the snuiU cyst.

Fio. 15.— Section through Ihi
retail. The ftiniiii:
tol. Uxi. IBOS.)

its diameters being 8.5 X 10 X 6.5 mm. ; the last diameter is that perpendicular
to the decidua basalis. The villi were covered by a Langhans layer (cytolropho-
blast) and a syncytium layer (spongiotrophobiast), and the cavity of the ovum
had a horizontal diameter of 7.5 X ^ mm.

Fig. 19 shows the embryonic structure after a model by Graf Spee (from
Kollmann's "Atlas"), and Fig. 20 a median sagittal section of them. The amnion

HUMAN EMBRYOLOGY.

Fio. 16.— Bcctioo throuah the embryonic strustuna of the Fra« trrum purios throuch the daB«Kl
membnoe {Kl. U.): the ■mnian it united with tbe chorion. AnlaceD of the blood-vewig WHmr in the
mennchymatoua tinua which produoM tb« unioa. XSO. (From Fnani: Anh. f. milcr. Anat.. vol.
U«.190a)

elion throucb the embryonic itructi:
. Tbe origin of the alteatoic duct (All. O.) fr
■Titr, and the belly etMk (£.».) with vaMul

: behind the cloaca]
lUd^ portion o( the
lion. X80, (From

Fio. 18. — Section (brousha portion of the wall of the yolk sack of the Fraui ovum. D.E.. epithe-
lium of the yotk wck; C. S., ccelomic epithelium. Between the calomic epithelium, which in (he recioD
■howD is high and rich in tinue Quid, and the epithelium of the yolk tack are anlagen of blood-veewle and
blood. The epilhelium ol the oelom over the aulacen of the blood-veesels is exactly like that linins the
email cyst at the lower pole of the yolk uck [Fig. 14a) and is diatinetiy differenl from that of the yolk
■Bck. X300. (From Fiaasi: Arch, f.mikr. Anat., vol. lui, 1008.)

OVA AND VERY YOUNG EMBRYOS. 39

is represented as opened in Fig. 19. The primitive streak, which occupied halt
of the germinal disk in the stage of development last described, is now limited
to its posterior end, and thb is bent strongly downward. At the anterior end
of the streak was a well-developed canatis neurentericus, and in front of this
the medullary groove bounded by well-formed medullary folds.

The greatest direct length of the embryonic structures, measured from
the anterior curve of the amnion to the attachment to the chorion before the
embryo had been placed in alcohol, was 2 mm., and that of the germinal disk from
the anterior curve of the amnion to the hind end of the primitive streak was
1.54 mm. Throughout this length the disk rested like a lid upon the yolk sack.
Tbe average diameters of the germinal disk (i.e., the distance in a direct line
between the lines of reflection of the germinal layers into the amnion and yolk
sack) were: anteriorly, 0.704-0.741 mm.; at the middle and posteriorly, 0.665 mm.;
in the region of the canalis neurentericus and primitive streak, 0.589 mm. ; and
in the region of the twliy stalk, about 0.4 mm. The medullary plate, disregarding
its curvature, presented its
greatest diameter of 0.517-
0.57 mm. anteriorly; at its
narrowest portion, about the
middle of the germinal di^,
it was 0.494 to 0,38 mm. in
breadth. The hei^t of the
belly stalk together with the
amnion was 0.722 mm., tbe

tuns of Spec's GlAeveelw ovum The head cDd ia toward ths

»..™. .... .,.. ,„. ,-,. l»'t- Gray, trophoblM^ bl«i, «tobl«l <rf th. embryo "d

II of the NonnenUtel ol Keibel and ■ninion; green, enloblut of the mloetioe and yolk e«lc. X 25.
ElM IBken from Kollmann'e Atl« ) {Adapted from Fia. 88 of KoUmann'a Atlss. From the Nor-

mentkfel of Keibel and Elie.)

width of tbe ectoblast plate exclusive of the amnion was 0.361 mm., and that of the
subjacent mesoderm mass was 0.209 mm. The lumen of the neurenteric canal was
0.024 mm. in diameter and that of tbe circular swelling seen surrounding it on
surface view was 0.13 mm.

Of this important embryo some figures are here reproduced, some of tbe
yet intact embryo as published by Spec in his paper of 1889 and some of
sections of it. Fig 21a shows the embryonic stnicture seen from tbe side as
an opaque object: K, the embryonic shield (germinal disk); D, a constriction
of the yolk sack; to the left one sees the caudal end of the embryonic shield

40 HUMAN EMBRYOLOGY.

bent down at right angles to the rest of the shield. Fig. 21b shows the dorsal
surface of the embryo, and in Fig. 21c it is diowii from the right and dorsally;
both these drawings were made under direct illumination, the amnion being intaet
bnt cleared with turpentine, while the germinal disk still remained opaque. The
reflection of the amnion into the embryonic shield is indicated by g; at the hiuder
end of the shield is the primitive streak (Psl) and in front of this is the opening
of the neurenteric canal. In Fig. 21c the portion of the streak that is bent
venlrally is also visible.

Figs. 22 and 22a represent a section passing tfarough the neurenteric canal ;
the amnion, the yolk sack, and the relations of the germinal layers are shown.
The distal portion of the yolk sack shows blood-vessels in course of development;
the round spaces shown in that r^on represent vascular canals lined with
endothelium and, for the most part, completely filled with young blood-corpuscles,
not shown in the figure. The diameters of the vessels increase toward the distal
surface of the yolk sack; on the right side the yolk sack was torn. Fig. 22& shows
the middle portion of the section represented in Fig. 22 more strongly magnified.

Fmb. 21»-e.— Thre* view* of the •mbryonic Mructurei of Gmf Bpee's GkacvedK ovum. Fi«.
21a. Lslenl virw^ K, the embryonie shield; D. ■ constriction of Ihe yolk sacli: to the right is Ibe caiuUl
end of the embryonic xhield which is bent downwards at riiht angles to the rest of the shield. Fig.
ZIb. Dorsal view. Fig, 21c. View taken dorsally and from the right. Am. amnion: C yolk sack;
F, medullary groove: tr. line of rEfleclion of Ihe aniDToa: Md. (Dedullary platei iV, caoalis neurenlericua;
PM. primitive streak. (From the NormeDtsfel of Keibe! and Else.)

Fig. 23 is of a section through the region of the medullary groove. The chorda
is included in the entoblast. The mesoblast shows to Ihe left a small cavity (h)
resembling the cavity of a primitive segment in process of formation, and to the
right is a narrow cleft in communication with the estra:-«mbryonic crelom.

Fig. 24 shows a section through the broadest portion of the head plate;
it shows already a tendency toward the closure of the intestine. The primitive
streak and primitive groove are represented more highly enlarged in Fig. 25.
At the primitive streak the ectoblast bends down to unite with the layer of
mesoblast subjacent to it. The nuclei of Ihe mesoblast are separated into two
layers by a strip (Z) destitute of nuclei and also by a contour line that quickly
disappears. The single layer that lies next to the entoblast cannot be distinguished
from that layer in the middle of Ihe section, and in this region the entoblast appears
thickened. P'ig. 26 shows Ihe half of a section passing through the medullary
groove, greatly enlarged; at P it^shows the appearance of the pericardial cleft.

The embryo described by Elemod, a model of which has been reproduced
by Friedr. Ziegler, is very similar to the Glaevecke embryo of Spec, but was not
as well preser\-ed. It was obtained from a woman who had cohabited only during
the night of November 6-7. The menslnaation expected on November 22 was
omitted, the abortion occurred November 28.

OVA AND VERY YOUNH EUBKYOS.

FlOB, Z2-26.-S^plioc

la Ihmugh the Glaevee:

lie embryo after Gra

f Spec, from t

Kribel soil ElK. .Im, snmii

m; Ch. chords; CI. pari.

clai layerot Ihemee

oblast; D. yoll

I sack;

a. viaeeial

ectoblMt: En. entobli

•St; F. medullary gr

•mnioD; Md. m«lull«ry plate; .Vi, nirsoblant; N, e

anaJi. neurenlerieus;

/■«, 'primitive

streak

.Ik sac:

k. Khieh are

iined with endotheli.™ Mid i

jBually packed with blood -cornustles. are reprcKnled an pierely r

pund space..

Fio, 221..— The middle of Ihe (eraun<a di»k of Fie 2^ more highly

msaiU6al,

Flo. 23.— Smtion thn

3u«h the region o[ the

h. a small cav

»vity; to the right . en

lall cleft apparenlly i

ionwi

th the extra-

Fio. 24.— Sfclion thr

Dugh the broadeat porti

on of the head plate.

Fio. 26.— Section thi

magnificaiion.

»lr«l.lhc«tobla«t bends di

jwn into the layer otth

e mesobiaat IJtff ) lying subjacent ti

)it. The nuclei of

Iht mesoblast are Mparsted .

ip (Z) deatilute of n

uclei and also

by a

that quickly diaappesn. In thia tiection the layer nei

.ttheentoblastcanne

Hbedistinguie

hedfrt

,m that layer

in the middle tine uid seems

to be thickened in that

region.

FtQ. 28.- 3«tion thn

3iigh the anterior legior

1 of the medullary gi<

ar^.

P. peri car-

dial dett.

42 HUMAN EMBRYOLOGY.

fn the fresh condition the entire ovum with its villi measured 10.0 X 8.2 X ^^
mm. The villi had a length of 1.2-2.0 mm., their diameter being 0.3-0.8 mm.
The embryonic shield was biscuit-shaped and measured in length from head cap
of the amnion to the projecting caudal end 1.3 mm.; its breadth was 0.23 mm.
in front and 0.18 mm. posteriorly. The closed amnion was continued into an
amniotic duct. Further it may be remarked that Etemod describes the remains
of a chorda canal in both the caudal and cranial ends of the chorda anlage,
which is flattened and contained within the entoderm. Etemod's statements con-
cerning the heart and the blood-vessels will be considered in the chapter dealing
with those structures.

Since Spec's Glaevecke embryo showed indications of the commencing
formation of the embryonic coelom and the primitive segments, it represents the
final stage of the period of development we are here considering.

V.

THE FORMATION OF THE GERM LAYERS AND
THE GASTRULATION PROBLEM.

By FRANZ KEIBEL, FRsiBUBa i. Br.

The formation of the germ layers, like the processes of
segmentation, has not yet been observed in the human species;
in the youngest known human ova the germ layers are already
present. The middje layer, it is true, is still in process of forma-
tion f rdii the primitive streak in the younger ova; but it is a
striking fact that in the very youngest ova, although a primitive
streak cannot be recognized with certainty, nevertheless the
middle germ layer is abun^Jantly present. I have not employed
the terms ectoderm, mesoderm, and entoderm— or ectoblast, meso-
l)last, and entoblast — ^because an accurate definition of them
caimot be given so long as the middle layer is still in the process
of formation; furthermore the nomenclature, influenced by theo-
retical considerations, is^ not altogether unambiguous and we must
first understand its significance.

If we would understand the conditions in man, or even approach to an
understanding of them, we must first briefly consider the corresponding conditions
in other mammals, then those of other vertebrates, and, indeed, those of the
invertebrates also. All the similarities that may be found in the processes back
of the formation of the germ layers in the vertebrates and invertebrates we must
regard as convergence phenomena, but with the formation of the layers we come
so near to the common origin of the two groups that we may well look for some-
thing directly comparable. The formation of the germ layers is not yet entirely
understood in mammals. Selenka ' described an immigration gastrula in Didelphys
rirginiana, and Van Beneden came to the conclusion that in the mammals the
material for the ectoblast and the entoblast or hypoblast was separated even at
the first segmentation division. The descendants of the ectoblast cell grew
around those of the hypoblast cell and so produced an epibolic gastrula, and the
region where the epiblastic cells finally closed over the hypoblast was regarded as
the blastopore; it was situated in the region at which the embryo later formed.
Van Beneden has now given up this hypothesis for sufficient reasons, but it has
been revived by Duval, who, however, places the closure of the gastrula at the
anti-embryonic pole. I believe, with Van Beneden, whose conclusions rest on
extensive observations, that Duval has been deceived by artefacts. Nor can I
regard Selenka's observation as certain. The material was very scanty and its

*For the literature, other than that which is directly cited here, see Keibel:
Die Gastrulation und die Keimblattbildung der Wirbeltiere Ergebnisse d. Anat.
u. Entwicklungsgesch., vol. x (literature to 1900), 1901.

43

44 HUMAN EMBRYOLOGY.

investigation does not seem to me to have been beyond criticism. If, for the
present, we disregard theories, we can say that in mammals there is formed by
segmentation a solid mass of cells, a morula, in which, in many cases, an outw
layer can be distinguished at an early stage from an inner cell mass. If this
outer layer is incomplete, the interruption occurs at the embryonic pole. At the
opposite pole the outer layer separates itself from the inner cell mass. Van
Beneden believes that this separation takes place by the vacuolation of the lower
cells of the inner mass, but it may also be supposed to occur by a simple separation
of the outer layer from the mass. There is thus formed, from a cell mass, a
morula, a small vesicle, a blastula; to the embryonic pole of this blastula is
attached a mass of cells, which, among other things, includes the actual embryonic
anlage.

On the under surface of this mass of cells there arises, by a process which
must be termed delamination, a layer of cells which will become the intestinal and
yolk-sack epithelium, that is to say, the entoderm. It may be formed at a time
when the cell mass still projects into the interior of the embryonic vesicle (as, for

Amn. H*
Amn n

Fio. 27. — Diacrams of the formation of the amnion aocording to the hedgehog-bat type. Amn. H^
unniotio cavity; Prtir., primitive streak. The prospective significance of the cells, even b^ore the germ
layers are delimited is represented in this and the following diagrams by colors. Black and gray, eetoblast
(jblack, eetoblast of the embryo and of the anmion; gray, trophoblast); green, entoblast; red, mesoblast.

example, in the deer) or when it has spread out to form the embryonic shield
(as in the dog), but these differences will be considered later. Here we must note
that with the appearance of this cell layer, which grows around the inner wall
of the embryonic vesicle and reaches the anti-embryonic pole sooner or later,
except in some cases, the mammalian ovum has reached the gastrula stage; it
consists of two layere or cell complexes, of which the inner one will become the
intestinal and yolk-sack entoderm.

As has been already mentioned, the development may take place in different
manners, even if those mammals which present a so-called inversion of the germ
layers be disregarded. We will follow it through thi*ee different types.

In the hedgehog, according to Hubrecht, and similarly in the bat, according
to Van Beneden, there is formed from the inner cell mass in addition to the
entoblast mentioned above (Van Beneden's lecithophore, the yolk layer of other
authors) an outer germinal layer, from which the eetoblast of the embryo and of
the amnion and the mesoblast are formed. This occurs, as is shown in Fig. 27, h,
by the appearance of a cavity in the round mass of cells shown in Fig. 27, a,
which cavity is directly transformed into the amniotic cavity; in its floor the
embryonic shield is formed, in the region of the embryonic shield the primitive
streak appears, and from the primitive streak the middle germ layer or mesoblast
arises. The development of the mesoblast and primitive streak in the different
tj^es will be discussed later and we may now consider the second tjrpe, shown by

GERM LAYERS AND GASTRULATION.

45

Amin.f

Fio. 28. — Diagrams of the formation of the germ layers and amnion in the deer (the ruminant and ing
type; mammals with entypy of the germinal area). Amn, F., amniotic folds: Prtr., primitive streak.

Prsfr.

Amn. F,

D

Fio. 20. — Diagrams of the formation of the germ lasrers and amnion in carnivores. Amn. F^ amniotic

fold; Prttr., primitive streak.

the deer and also by the sheep and pig. In the deer, as in the hedgehog and hat,
a cavity is formed in the inner cell fnass (Fig. 28, c), but this cavity does not
remain closed and is not directly transformed into the amniotic cavity; it opens to
the exterior, the embryonic shield flattens out upon the surface of the ovum,
and the amnion is formed from a fold that rises around the embryonic shield.

46 HUMAN EMBRYOLOGY.

A third type (Fig. 29) is foiiud, for example, iir-the dog and other mammals, and
in it the inner cell mass flattens out to fonn th^ embryonic shield before the
entoblast appears; from the beginning the embryonic shield is spread out upon
the surface of the ovum, and in the rabbit it is at first covered by a thin layer of
cells (Rauber's covering layer), which soon disappears. A fundamental difference
between these three types does iiot exist, nof does it exist in the so-called inversion
of the germ layers which may be observed in many rodents. The mode of develop-
ment of mammals showing this inversion is readily intelligible if one takes as a
starting point for it the first type of development described above (that of the
hedgehog and bat, Fig. 27). In Fig. 30 are two diagrams. which will make clear
the so-called inversion. In Fig. 30, a, the two-layered ovum has become invaginated
into itself and the invagination opening has become closed by a trophoblast growth.
Fig. 30, b, shows the formation of the mesoblast and the amnion.

Opinions regarding the development of the mesoblast in mammals are still
very divergent. Ortain it is that the primitive streak is its principal seat of

Amn. F,

Prttr.

Fig. 30. — Diagrams of the for-
mation of the amnion in cases of
inversion of the germ lajrers (sim-
plified!). Amn. F., amniotic fold;
Pratr., primitive streak.

formation. It arises from the primitive node, a thickening of the upper germ
layer, from which the mesoblast cells grow out between the upper and lower germ
layei*s. But whether this jDrimitive node appears within the limits of the em-
bryonic shield and the primitive streak is formed by a growth from it directed
caudally, or whether the primitive node appears at the caudal end of the embryonic
shield and the primitive streak is formed by a forward growth from it — these are
questions concerning whose answers there is still difference of opinion; this is true
also as to the question whether the primitive streak is the only source of formation
of the mesoblast. Bonnet, for example, recognizes two other sources. He believes
that a mesoblast area surrounds the embryonic shield, the mesoblast in this area
being formed from the inner germ layer. He described this area in the sheep,
but could not find it in the dog; and it is certain that it does ti6t occur in a
number of other mammals. A second source of the mesoblast from entoblast
Bonnet finds in the " completing plate " of the primitive gut cord. It lies in
the anterior region of the head and from it, in addition to a premandibular rudi-
ment of the gut, there arise the chorda and the mesoderm of the head region.*

'Although it is impossible to consider here the various individual opinions
regarding the formation of the mesoblast in manmoals, nevertheless the observa-
tions of Wilson and Hill (J. T. Wilson and J. P. Hill: Observations on the
Development of Omithorhynchus, Philosph. Transactions, Ser. B. vol. cxcix, 1904)
on Omithorhynchus may be considered. In their opinion the primitive node, which

GERM LAYERS AND GASTRULATION. 47

At the height of its development the mammalian primitive sireak extends
throughout almost the entire length of the embryonic shield, beginning a short
distance behind its cranial end and extending to the caudal end ; later it degenerates
in a craniocaudal direction. At its cranial end a canal, the canalis neurentericus,
which traverses the embryonic shield, may be formed; its caudal end gives rise to
the cloacal membrane. From it there is formed a large portion of the body of the
embryo, for, in my opinion, there can be no doubt but that it originally extends
far into the head region; its anterior end and the neurenteric canal, when it is
present, migrate, therefore, in a craniocaudal direction. From the axial mesoblast
which is thus formed in front of the anterior end of the primitive streak the chorda
arises, from the more lateral mesoblast the primitive somites and the mesoblast of
the embryonic body situated still more peripherally.

The chorda anlage is transitorily enclosed within the entoderm, but later it
again separates from it. For a time the growth of the primitive streak keeps pace
with the amount of material separated off from it; but later the streak becomes
gradually smaller, giving off more material than is replaced by growth, and, finally,
it becomes transformed into a region of proliferation which is usually termed the
tail bud, but which also gives rise to a portion of the body. This region of
proliferation consists of an indifferent cell material into which the medullary tube,
the chorda, intestine, and mesoderm pass and from which the caudal portions of
these structures are differentiated.

A sharp distinction cannot be drawn between the primitive streak and the
tail bud; but« since the tail bud is distinct as such even in mammalian embryos
with less than twenty primitive somites and the degeneration of the primitive
streak is in full swing in still younger embryos, it would perhaps be better to
speak of a trunk bud than of a tail bud.

Having thus learned how the germ layers are formed in the mammals we
may now inquire how their formation compares with what occurs in other animals;
in other words, we now come to a consideration of the theories generally known
as the gastrulation and the coelom theories. And here we must first agree upon the
definition which is to be applied to the process of gastrulation. The inconsistent
and frequently actually contradictory definitions that have been given of gastrulation
have so obscured what is in itself a difficult question, that it is not easy to give an
account of it. The anatomists and purely vertebrate zoologists are to blame for
some of the difficulty, in that they have not perceived that the process of gastru-
lation is not something confined to the vertebrates, but, as the fundamental works
of Ray Lankester and Haeckel have shown, is a process which occurs in the
majority of metazoa. Hubrecht has rendered good sendee by energetically point-
ing out that it is not permissible to define gastrulation differently in the vertebrates
and in the other metazoa; and I am thoroughly in agreement with him in this,
even although I considered the question for many years entirely from the stand-
point of a vertebrate zoologist. Accordingly, I define gastrulation as the process
by which the cells of the metazoan ovum are separated into an upper and a lower
layer, into ectoblast (ectoderm) and entoblast (hypoblast, entoderm), and by
entoblast I mean only the cells forming the intestinal epithelium.* That we must
regard the final result as the most important thing in the idea of gastrulation and

marks the position of the blastopore, comes into relation with the primitive streak
only secondarily; originally it lies outside the embryonic shield. Yet it seems
to me questionable if the structure which the authors regard as the primitive node
in early stages is the same structure which they so designate in later stages; I
have wondered whether the primitive node of younger stages may not be the
yolk navel.

' The intestine here includes its appendages, the yolk sack and the intestinal
glands.

48 HUMAN EMBRYOLOGY.

must disregard the manner in which this is brought about (delamination, immigra-
tion, invagination, epibole) I had already pointed out before Hubrecht, and had
shown that the processes that had usually been designated as gastrulation in the
vertebrates could not be directly compared with the gastrulation processes of the
invertebrates. I must, therefore, consider the question here so far as is necessary
for the understanding of the nomenclature and the older literature, and for further
details would refer to my paper of 1901 already cited and to the explanations by
Hubrecht,* myself,* and Brachet."

The entire theory of the formation of the germ layers and gastrulation in the
vertebrates is based upon the development of AmphioxtM. In this form the material
for the formation of the intestinal entoderm, the mesoderm, and the chorda is
laid down in the interior by a single process, and for a long time all investigators
have incorrectly designated this entire process as gastrulation and have started
their ccHisideration of gastrulation in the vertebrates from it. In the same way
in 1901 I defined gastrulation, pointing out, it is true, that the definition could
only apply to vertebrates, as the process by which the cell complexes for the
intestinal entoderm (i,e,, intestinal and yolk-sack entoderm), the mesoderm, and
the chorda were brought into the interior of the ovimi. I stated, further, that
this definition could be extended to all vertebrates if two phases were recognized
in it: a first phase in which the intestinal entoderm, and a second, in which the
mesoderm and the chorda were formed. If one assumed that alterations in the
true relations of these two phases occurred, all variations could be explained and
the common basis for both processes could be recognized.

I had come to this conclusion in 1889^ as the result of studies in the
development of manmialia, and at about the same time Hubrecht* also reached it
independently. I have since carried the idea further and will here refer to some
of the points which I brought together in my observations and conclusions in
1893.* I said then:

" In the mammals gastrulation takes place in two phases. In the first phase
the lower germ layer, the entoderm of authors, is formed; in the second phase
the chorda and mesoderm. From the so-called entoderm of the mammals there is
formed essentially only the intestinal epithelium and that of the yolk sack. That
additions are made to the intestinal epithelium from the cell mass which is formed
in the interior of the ovimi during the second phase of gastrulation cannot be
absolutely denied ; but in any event these additions, * if they actually occur,' are
insignificant and are limited to a small region of the intestine. In the other
anmiotes gastrulation also occurs in two phases, yet the cell complexes formed
in the interior of the ovum by the two gastrulation phases do not exactly correspond
either qualitatively or quantitatively in different forms: thus in the Reptilia,
and especially in the Chelonia, the second phase of gastrulation carries into the
interior of the ovum the whole, or at least a considerable portion, of the intestinal
epithelium; while in the mammals the intestinal epithelium, together with that

* A. A. W. Hubrecht : Die Qustrulation der Wirbeltiere, Anat. Anz., vol. xxvi,
1905.

*F. Keibel: Zur Gastrulationsfrage, ibid.

• A. Brachet : Gastrulation et formation de Fembryon chez les chords, ibid.,
vol. xxvii, 1905.

*F. Keibel: Zur Entwicklungsgeschichte der Chorda, Arch. f. -Anat. u.
Physiol., Anat. Abt., 1889.

•A. A. W. Hubrecht: Die erste Anlage des Hypoblast bei den Saugetieren,
Anat. Anz., 1888, vol. iii, pp. 906-912; and The Development of the Germinal
Layers in Sorex vulgaris , Quart. Joum. Micr. Sci., vol. xxxi, 1890.

•F. Keibel: Studien zur Entwicklungsgeschichte des Schweines, Schwalbe's
Morphol. Arb., vol. iii, 1893.

GERM LAYERS AND GASTRULATION. 49

of the yolk sack, gaijis its definitive position during the first phase.'* Later obser-
vations, however, show that reptiles more closely approximate the mammals in this
respect, and it is becoming more probable that in the Reptilia also the lower
layer, usually termed the paraderm, yolk layer, or secondary entoderm, gives
origin to the intestinal epithelium."

Concerning the gastrula cavity I said:

" The gastrulation cavity of the first phase of gastrulation, if it is formed
at all, fuses very early, or immediately, with the segmentation cavity in mammals;
but probably it does not occur at all.

" The cavity of the mammalian ovimi in the two-layered stage is, conse-
quently, to be regarded as the sum of a portion of the gastrula cavity and a
portion of the segmentation cavity. Another portion of it is to be found in the
cleft between the two primary germ layers. Con*esponding conditions, which I
shall for the present regard as merely analogies, occur in the Amphibia. In birds
and reptiles the germ, or subgerminal, cavity is also to be considered a portion of
the gastrula cavity, and a portion of the segmentation cavity. A second portion
of this latter cavity in the Sauropsida is also the cleft between the upper and
lower layers of the two-layered germ.

" The chorda cavdty of mammals is to be regarded as a part of the gastrula
cavity and belongs to the second phase of gastrulation. Only exceptionally are
cavities found in the second phase which can be considered as remains of the
ccelomic diverticula of the archenteric cavity.

" In the mammals the primitive streak is to be regarded as equivalent to
the blastopore. In the germinal ring of the germinal disk of the birds and reptiles
I also see a homologue (morphologically equivalent part) of a portion of the
blastopore; it has, of course, been extremely modified."

These views have, it is true, not been unopposed, but since they have been
reproduced in O. Hertwig's " Handbuch " and in his " Lehrbuch " and his
" Elements," they may be regarded as the prevailing ones. How they must be
modified if we are to make use of the definition given above, which applies to
all metazoa that have an intestine, must now be considered. In the first place,
it may be said that the separation of the gastrulation process into two phases
has not been without results. What I have hitherto termed the first phase of
gastrulation in the vertebrates, and especially in the mammals, must now alone be
regarded as gastrulation, and the process which I formerly termed the second
phase of gastrulation, that is to say, the formation of the mesoderm and chorda,
since there is nothing directly comparable to it in the invertebrates, or, at all
events, nothing comparable that can be regarded as belonging to gastrulation,
must be separated from that process and regarded as a process by itself, even
although it has become intimately associated with or even, so to speak, included in
gastrulation as the result of a shifting in the time relations. But with this formal
separation of the two processes and the simple modification of the nomenclature
we have not yet reached perfect clearness, difficulties still remaining as to the
homologue of the blastopore. In my earlier definition I compared directly the
primitive streak of the amniotes with the blastopore; but this will not now hold,
since the characteristic of the invertebrate blastopore, the direct transition from
ectoblast to entoblast, no longer obtains in the amniotes. Between the ectoblast
and entoblast there is interposed in the primitive streak the mesoblast, derived

"Greil (Ueber die erste Anlage der Gefasse und des Blutes bei Holo- und
Meroblastiem [speziell bei Ceratodus forsteri], Verb. Anat. Ges., 1908) states
(p. 58) that it "must be recognized that in the first phase of Hertwig and other
authors there is formed not the entoderm of the entire embryonic anlage but only
the abortive entoderm of the yolk sack." This is certainly incorrect for mammals
and birds, and probably for the reptiles also.

4

50 HUMAN EMBRYOLOGY.

from the upper germ layer, and the streak also gives rise to the chorda; indeed,
we may say that for a time, in early stages, the chorda arises directly from the
upper layer. We can compare with the blastopore only the line of junction of
the entoderm with the mesoblast and chorda, where such a line exists; and if we
are to make comparisons with the invertebrates we must regard the mesoderm
and chorda as products of the upper genn layer, the ectoblast."

What has hitherto been designated as the blastopore in the vertebrates,
Amphioxus included, lies in the territory of the ectoblast and its derivatives and
not at the boundary between ectoblast and entoblast; this structure, which un-
doubtedly resembles the blastopore most closely, but can only be compared with
it at its first formation, is comparable to the primitive streak. Furthermore, the
vertebrate body is formed not by the simple conversion of the gastrula into it,

in-

m.5^

an

Fig. 31. — Young Trochophvra of Polygordius Fio. 31a. — Older Trochophora of PoIygordiuB.

in which the body is beginning to grow out. an. The body region has grown larger and a number of

anus; m, mouth; ms, mesoderm; «p, apical plate. segments have formed in the mesoderm, an, anus;

(Simplified from Hatschek, from Jablonowski: m, mouth; ma, mesoderm; «p, apical plate. (From

Anat. Anz., vol. xiv, 1898.) Jablonowski: Anat.Ans., vol. xiv, 1898.)

but a budding zone is formed in the region of the blastopore from which the
segments of the vertebrate body are budded off. At this stage a comparison
with the Trochophora (Fig. 31), a widely distributed lan^a among the annelids and
molluscs, is quite possible, as Kopsch" and J. Jablonowski" have shown. Just
as we can distinguish in the body of the larva an anterior unsegmented portion

"This has already been done quite logically by Lwoff (B. Lwoff: Ueber
einige wichtige Punkte in der Entwicklung des Amphioxus, Biol. Zentralbl. vol. xii,
1892; and Die Bildung der primaren Keimblatter und die Entstehung der Chorda
und des Mesoderm bei den Wirbeltieren, Bull. Soc. Imper. des Natural, de Moscou,
1894) in the case of Amphioxus, He regards as the principal result of his in-
vestigations the conclusion that " in Amphioxus the invagination is in no wise to
be regarded as a simple gastrulation, as has hitherto been done. There are, rather
two different phases to be distinguished in it: in the first place, the invagination
of the entoderm cells, from which the intestine is formed; and, in the second
place, the invagination of ectoderm cells from the dorsal transition border, which
form the ectoblastogenic anlage of the chorda and mesoderm."

" Kopsch : Gemeinsame Entwicklungsf ormen bei Wirbeltieren und Wirbellosen,
Verb. Anat. Ges., 1898.

" J. Jablonowski : Ueber einige Vorgange in der Entwicklung des Salmoniden-
embryos und ihre Bedeutung f iir die Beurteilung der Bildung des Wirbeltierkorpers,
Anat. Anz., vol. xiv, 1898.

GERM LAYERS AND GASTRULATION. 51

which has been formed by the gastnilatioa process, and a posterior segmented
portion which owes its existence to a budding process that succeeds gastnilation,
so too is it possible in the vertebrate embryo. Hubrecht consequently distinguishes
between cephalogenesis and notogenesis in the development of vertebrates. By
cephalogenesis the anterior uns^mented portion of the vertebrate body is formed
as a result of gastrulatton ; by notogenesis, a process of budding, the succeeding
portion is formed. One must not, however, misunderstand these expressions. The
limits of the two portions of the body must not be sought where the head
now joins the trunk; trunk segments in unknown number have been taken up
into the head and " the question concerns, on the one hand, only the most anterior
region of the head, to which the olfactorius and opticus belong; and, on the
other hand, the remaining portion of the brain, together with the base of the
skull with the remains of the chorda and the visceral arches, and the entire trunk."

Fia. 32. — a, gutrula with open bluitopon; b, a radially symmetriol sctiniaD-like ocelentarKU dia-
cram: c. a bilaUndly >yrametriail, eloogste. worm-like, aod kctiniui-like uiimal wilh ■tomodttum and
cut pouches; c^ ■ worm-like protoshonliite wilh diCTenntistion of a head, trunk, and chorda, and witha
b^innini malametiam. <From Uubreoht: Anat. Ana., vol. xxvi, 190S, Fici 3-6.)

While it is far from my intention to attempt a derivation of the vertebrates
from the actinite at all directly, yet it may be well to consider the possibility of
derivation from such simple forms. With this object I give here Hubrecht's
speculations (Quart. Joum. Micr, Sci., vol. xHx, p. 410) (Fig, 32) ; " Once the
didermic gastmla-stage reached, a second phase of ontogenetic development is
inaugurated which is also of higli phylogenetic importance. In this phase the
bilaterally symmetric metameric animal gradually appears which we have to com-
pare with possible phylogenetic transition forms that have connected the Vertebrates
with radially symmetrical ancestors. This attempt at a plausible and rational
reconstruction of the Vertebrate ancestry is, of course, hampered by the circum-
stance that no trace of those forms is any longer in existence. Still, an actinia-like,
vermiform being, elongated in the direction of the mouth slit, imposes itself upon
our imagination, such as has served for the theoretical speculations of Sedgwick
on this same subject, and has once been accepted by van Beneden for the precursors

52 HUMAN EMBRYOLOGY.

of the Chordata." Hubrecht has pointed out that " the processes of growth by
which a Coelenterate gastrula becomes fixed and gradually changes into a sessile
Actinian can hardly be looked upon as protracted phases of gastrulation. This
will be more difficult yet when the animal has already acquired a higher degree
of complication than that of the Ccelenterates, and swims about in the shape of
a worm-like, lower chordate animal. We know of Polygordius and of other primi-
tive worm types that to the radial, didermic larval stage — the Trochophora — an-
other developmental phase succeeds, during which we obsen^e proliferation in the
anal region, leading to an increase in the distance between the anus and the apex
of the metamerical worm, the latter budding off, so to say, from the radial
trochophora.

" We find similar processes in the Vertebrates, but without a free trochophora
larva, and to this latter radial and didermic primitive stage corresponds in the
Craniata the rapidly passing earliest phase in which delamination calls forth two
germinal layers. Both in Elasmobranchs and in mammals we notice that the
cellular material which is present in those very earliest stages contributes especially
— as it does in the trochophora — towards the formation of the anterior part, the
head, and that, following upon this, a proliferation-process is inaugurated (com-
parable to the origin of the metamerical worm out of the trochophora larva) by
which the notochord and the somites, i.e,, the bilaterally symmetrical metameric
animal, are called into existence."

Hubrecht, going far back in the phylogeny, compares this proliferation with
the growth of an elongated actinian. He imagines the coBlom pouches of the
actinian, still in communication with the intestine, to represent the somites; the
nerve ring on the oral disk would represent the spinal cord; the stomodseum, the
chorda; and the actinian mouth, which is not to be regarded as its primitive mouth
or blastopore, but is a secondary formation, represents the primitive streak, that
stands in such intimate relation to the chorda (that is, to the actinian stomodseum).

The ingerent opening of the actiniaa gastrula elongates to form the actinian
mouth that leads into the stomodaeum; the blastopore of the mammalian gastrula,
which never opens, elongates posteriorly to form the primitive groove, whose floor,
the primitive streak, furnishes the material for the chorda.

" There is, then, during ontogeny an unbroken continuity between the blasto-
pore of the Actinian and its oral slit, between the blastopore of the Vertebrate
(often only potential in mammals and not identical with the opening that is called
by that name in Sauropsids) and its primitive groove. A phylogenetic continuity
has to be statuated between this oral slit of the Actinia and the peculiar spot (be-
hind the so-called anterior lip of the blastopore) which on the Vertebrate embryonic
shield gradually moves backwards and establishes in many cases an open communi-
cation between a portion of the Vertebrate intestine and the exterior. The primitive
streak, however, the solid material that proliferates downwards from the ectoderm,
coalesces with the entoderm, and brings forth the notochord from its median (though
really paired) portion and the somites from its lateral wings — this primitive streak
can never be identified with a blastopore. For we have above attempted to demon-
strate that in this primitive streak we encounter the material which, also in the
Actinia, (1) proliferates downwards from the ectoderm and produces the stomo-
daBum, (2) coalesces with the entoderm, (3) is in direct continuity with those parts
which are preparing to give rise to coelomic pouches but are yet continuous with the
primitive enteron." Hubrecht proposes a modification of the nomenclature in that
for that portion of the vertebrate embryonic disk which he has compared with the
actinian mouth and stomodaBum he suggests the use of the name " dorsal mouth "
instead of primitive mouth, gastrula mouth, or blastopore. In this manner the
contrast with the phyla of the annelids and molluscs will be more plainly brought
out.

GERM LAYERS AND GASTRULATION. 53

If now we summarize what has been stated above and apply it to the
formation of the germ layers in the mammals, we must say :

1. In the TnRmmRls the entoderm (yolk and intestinal entoderm) is formed
by delamination ; and it is only this delamination process that one can term
gastrulation. The two cell-complexes which are formed as the result of gastru-
lation are to be termed ectoblast (ectoderm) and entoblast (hypoblast, entoderm).
That the superficial layer of the wall of the embryonic vesicle, for a time the only
layer that is present, must also be regarded as a portion of the ectoblast seems self-
evident; the so-called covering layer belongs to it also. In so far as it is con-
cerned in the nourishment of the ovum it may be termed, following Hubrecht, the
trophoblast. As trophoderm — in the sense in which that word is used by Minot —
a portion of the trophoblast is again to be distinguished, which in certain cai^s
produces the penetration of the ovum into the wall of the uterus. Morphologically
the trophoblast may be divided into the cytotrophoblast, from which the Langhans
layer of cells is formed in the human ovum, and the spongiotrophoblast (plasmodi-
trophoblast), which gives rise to the syncytium.

2. A typical blastopore has not yet been certainly observed in the mammals.
An invagination blastopore need not be expected to occur; some observations by
which a connection of the ectoderm and entoderm was shown in early stages,
before the formation of the mesoblast, have suggested the occurrence of a rudi-
mentary blastopore. The primitive node and primitive streak — whether or not a
primitive groove forms in the primitive streak is a matter of subordinate impor-
tance— are certainly associated with the blastopore, but cannot be directly homol-
ogized with it.

3. The anterior end of the primitive streak, at the time when the streak is
at its greatest extension anteriorly, but not always its most anterior part, must be
regarded as indicating the position of the blastopore.

4. The invagination processes by which in the mammals the formation of
the chorda and mesoblast is initiated, are comparable to the corresponding processes
in Amphioxus, but can be regarded as the gastrulation process neither in Amphioxus
nor the vertebrates. We must accordingly say that the chorda and mesoblast
arise from the ectoblast, the chorda partly directly and partly after it has be-
longed to the mesoblast for some time. The enclosure of the chorda in the
entoblast is an entirely secondary phenomenon.

5. Even although the region of the primitive streak, with or without a
primitive groove, cannot be compared directly with the fused lips of the blastopore
of a gastrula, nevertheless they must be regarded as modified structures that have
arisen in association with a typical blastopore and must be compared with what
it has been the custom to call the lips of the blastopore in the vertebrates, from
Amphioxus upwards. The processes which are here concerned are comparable
to the budding processes which in the Trochophora larva succeed the gastrulation
processes. This becomes especially clear when one considers the later transforma-
tion that the primitive streak undergoes and by which it becomes converted into
the so-called " tail bud," a structure from which (as has already been pointed out)
not only the tail arises, since the line between the tail and the trunk is merely
conventional. The principal limit that concerns us here lies far forward in the
head region, between those portions of the body which are formed by the gastrulation
process and those that owe their existence to the succeeding proliferation process.
The anterior end of the primitive streak, at the time of its greatest anterior
extension, marks this limit.

There result from these theoretical considerations certain conclusions that are
of interest from the more practical side. A longitudinal splitting of the embryo,
which may extend into the head region, may, under some circumstances, be regarded
as produced by inhibition of growth, which can be referred to the primitive streak
and the processes which take place in it.

54 HUMAN EMBRYOLOGY.

Roux's hemitheria anteriora such as the calf studied by Roux's pupil Eck-
hardt/* which Roux regarded as due to the early degeneration of the two seg-
mentation cells which contained the anlagen of the caudal half of the body,
are much more probably due to disturbances in the territory of the primitive
streak. According as these occur early or late, a greater or smaller fK)rtion of
the posterior extremity of the body will be wanting. Bob-tailed cats and dogs
also belong to this class of developmental inhibitions; in these the inhibition first
occurred after a portion of the tail had developed from the tail bud.

Embryology throws light upon the occurrence of coccygeal tumors and
their varied structure by the fact that in tlie " tail bud " an indifferent cell
material is present from which all the germ layers may be produced.

In conclusion, we may now return to man and endeavor, from
what we at present know concerning his development and that of
animals, to form a picture of the formation of his germ layers.
We must assume that the human ovum, similarly to that of the
guinea-pig, burrows into the mucous membrane of the uterus,
destroys the maternal tissues, and so makes a cavity for itself.
At the time of the penetration into the mucous membrane the
diameter of the ovum can scarcely amount to 0.5 mm. Very early,
but probably only after the ovum has burrowed into the mucous
membrane, the formation of the coelom and of the germ layers
begins. I assume that this formation can begin only at that time
because the burrowing process would otherwise encounter diffi-
culties from the enlargement of the ovum made necessary by the
formation of the coelom and mesoblast ; and it may also be supposed
that those cells would first be formed which are intended for the
destruction and absorption of the maternal tissue, the trophoblast
cells, which belong to the later ectoblast complex. At all events,
one must assume, as Spee pointed out as long ago as 1896, and
as is now rendered almost certain by the Peters ovum, that at the
time of the first formation of the mesoblast the diameter of the
ovum does not exceed 0.5 mm.

The formation of the mesoblast follows immediately upon
that of the amniotic (medullo-amniotic) cavity and that of the
cavity of the yolk sack and intestine. That the coelom in the
human ovum is formed by a splitting process is indicated by the
scattered mesoblastic strands which stretch between the yolk sack
and the chorionic mesoblast, as well as by observations in many
other mammals.*^

The human ovum is, consequently, to be assigned to the
category of schizocoel ova. It is, however, not yet quite clear
how the cavity traversed by scattered strands of mesoblast and
lying between the yolk sack and the chorion in the Peters ovum is

14

U

Eckhardt: Ueber Hemitheria anteriora (Roux), Dissert., Breslau, 1889.

This process may now be regarded as certain as a result of the observations
of Bryce and Teacher (he), which were published only after the first chapters
of this " Handbook " had already been written and which must be noticed
subsequently.

GERM LAYERS AND GASTRULATION. 55

to be interpreted. It may be supposed to represent the extra-
embryonic eoelom ; but it may also be imagined that it has arisen
from an extensive loosening up of the tissue and not by a splitting
of the mesoderm, and that the triangular space beside the caudal
extremity of the embryo (see Fig. 96, p. 108, in the chapter on
the development of the egg membranes and the placenta tion),
which is lined with flat cells having an epithelial arrangement, is
the first anlage of the eoelom.

As to the amniotic (medullo-amniotic) cavity, it may be said
with a probability bordering upon certainty that it arises by a
splitting of a solid cell mass; consequently, amniotic folds never
occur in man. The amniotic duct or cord — a connection between
the epithelium of the amniotic cavity and the surface of the
chorion, indications of which have been observed by Eternod and
Marchand and more distinct evidence by Beneke in himian ova and
by Selenka in apes — appears to arise later, and, indeed, it is ques-
tionable if it is of regular occurrence ; it is a phylogenetic memory
from dim ancestral times. Selenka (1903) believes that this
amniotic umbilicus, as he calls it, following Bonnet, does not
reach complete development in apes; that may also be the case
in man; at all events it is wanting in the youngest stages yet
observed, and, if it is of constant occurrence, its existence must
be limited to a very short period of time.

As the amniotic (medullo-amniotic) cavity, so also the cavity
of the yolk sack is formed by the splitting of an originally solid
mass of cells; in the Peters ovum it is still so small — smaller than
the ripe ovarian ovum — that one can hardly imagine it to be
formed by being enclosed by a surrounding epithelial lamella of
entoblast. No important difficulties stand in the way of its origin
by a splitting process.

Graf Spee in his paper of 1889 makes use of ova which
present an inversion of the germ layers for an explanation of the
conditions which obtain in the human ovum.

On the other hand, I maintained (1890) that the peculiarities
of the himian ovum were to be explained by the early formation
of the extra-embryonic eoelom and of the amnion, and that a
sinking of the human embryonic anlage deep into the yolk sack,
as in ova with inversion of the germ layers, could not be imagined.

In the endeavor to obtain a clear picture of the processes
just discussed, the extraordinary minuteness of the embryonic
structures must constantly be borne in mind. The diameter of the
yolk sack in the Peters ovum is 0.19 mm., that is to say, it is not
quite the size of a ripe human ovum.*®

" According: to Kolliker and Ebner (" Handbuch der Gkwebelehre," 6 Aufl.,
vol. iii, 1902), the diameter of the ripe human ovum is 0.22-0.32 mm.; and
Waldeyer remarks in Hertwigr's "Handbuch." concerning this statement, that he
has never seen human ova measuring more than 0.25 mm.

56 HUMAN EMBRYOLOGY.

Elze and I have endeavored in our * * Normentaf el zur Ent-
wicklungsgeschichte" to embody the results of the above con-
siderations in a series of diagrams. Fig. 33, Ay represents an
ovum towards the end of segmentation as a whole object. Fig.
33, B-Fy are sections, and it is assumed that all sections pass
through the median sagittal plane of the future embryo. The
figures are of such a size that they may be regarded as enlarged
twenty-five times. The ovum shown in Fig. 33, A, is still sur-
rounded by the zona pellucida; it may have just reached the
uterus. B represents an ovum which has already eaten its way
into the mucous membrane of the uterus. Four groups of cells
are to be recognized in it. The periphery consists throughout of
ectoblast cells — the trophoblast, represented in gray. Inside this
trophoblast mantle are three cell-complexes. That which gives
rise to the ectoderm of the embryo and of the amnion is repre-
sented in black; to the right, corresponding to the caudal end
of the later embryo, we have left indistinct the boundary between
it and the mesoblast complex, represented in red, in order to
indicate that in this region there is perhaps a transition between
the two complexes. We have represented this connection in the
diagram, because wherever the development of the mesoblast has
been sufficiently studied, the greater portion of it, at least, is found
to arise from the ectoblast complex, and we find later, even in human
ova, a primitive streak. It is extraordinarily difficult to picture
to oneself how the processes actually take place in man, owing
to the minuteness of the human ovum at this stage. The meso-
blast complex is everywhere forcing the entoblast complex, repre-
sented in green, away from the trophoblast shell.

Fig. 33, C, shows an older stage. By a process of splitting
in the ectoblast and entoblast complexes, the amniotic (medullo-
amniotic) cavity in the one case and the cavity of the intestine
and yolk sack in the other have been formed, and in a similar
manner the extra-embryonic coelom has formed in the mesoblast
complex. We have already pointed out that another mode of
formation of the coelom is possible. In this case we must suppose
that in this stage the extra-embryonic coelom is not yet formed
and we must imagine the cavity inside the red, which is left white
in Cy to have a pale reddish tinge and to represent solid but very
loosely compacted mesoblast. Around the amnion, the yolk sack,
and at the periphery next the trophoblast, the mesoblast, which
as a whole is still solid, is somewhat denser. The amnion at this
stage may still be in contact with the trophoblast shell.

Diagram D, Fig. 33, shows the conditions which obtain in the
Peters ovum. The trophoblast mantle surrounding the ovum has
developed lacunae which are filled with maternal blood, and the
mesoblastic axes of the villi have begun to grow out into the

GERM LAYERS AND GASTRULATION.

Fia. 33. — St*CM in the davalopment o[ germ layen. Orav. trophoblast; blatk. embrronic and
otic ectoblui: omn, iaUntinBl uid yo1k-<»ck ectoblut; red, meaoblait. a, ciBuiaJ end: p. csudal
X £5. (From Keibel ud EIm^ Nomieiiufcl. p. 13. Fig. 2>-f.}

58 HUMAN EMBRYOLOGY.

trophoblast. At the caudal extremity the belly stalk has become
distinct, but an allantoic duct is not yet formed. Whether or not
a very small primitive sireak was- present in the Peters ovum
must remain doubtful; we assume that the delimitation of the
ectoblast from the mesoblast was not quite sharp at the caudal
end, and this we take to be the anlage of a primitive streak. The
embryonic coelom is represented as completely formed, although
a somewhat different interpretation of the conditions in the Peters
ovum has been mentioned. The ectoblastic covering of the
embryo and the amnion are everywhere being forced away from
the trophoblast by mesoblast cells.

Diagram E, Fig. 33, represents a median sagittal section
through an ovum of the stage seen in the Frassi ovum. The
anterior half of the section, in the region of the embryonic shield,
is occupied by the floor of the medullary groove; behind it is the
neurenteric canal; and then, lying in the same plane as the
anterior half of the embryonic ^nield, the region of the primitive
streak, which occupies about b&lf the shield. At the caudal end
of the priim4;iye streak th^ feioacal membrane is already recog-
nizable. The chorda-ts' enclosed within the entoblast; anlagen of
blood and blood-vessels occur in the yolk sack. An allantoic
duct is present.

Diagram F shows a median sagittal section through the stage
seen in Spee's Glaevecke embryo. Especially to be noted is the
recession of tTie primitive streak and the fact that the now quite
short primitive streak is bent down at an angle to the plane of
the cranial extremity of the embryonic disk. A cloacal membrane
must have been present at the caudal end of the primitive streak,
but it is not represented in the diagram because it was not
observed in the Spee embryo, probably on account of the direction
in which the sections were made.

;

-• «*

VI.

SUMMARY OF THE DEVELOPMENT OF THE HUMAN

EMBRYO AND THE DIFFERENTIATION

OF ITS EXTERNAL FORM.

Bx FRANZ KEIBEL, FREiBincG i. Bb.

The first relatively satisfactory synopsis of the development of
the external form of tiie human body is that given by His ^ in his
"Anatomie menschlicher Embryonen" and in the Normentafel
published with it. In the latter there is shown a series of human
embryos dating from the end of the second week to the end of the
second month. With this latter period the development of the
embryo is so far advanced that the human in it is recognizable
even to the laity ; His designates this as the embryonic period and
that succeeding it up to birth he terms the fetal period. A com-
prehensive account of the development of the body during the fetal
period, with abundant illustrations, has been given by Gustav
Retzius^ in his memoir **Zur KenntAis der Entwicklung der
Korperform des Menschen wahrend der fetalen Lebensstufen,"
published in 1904.

Disregarding studies of individual embryos there must also
be mentioned here the ** Normentafel zur Entwicklungsgeschichte ' '
of Keibel and Elze,^ Carl RabPs ^'Entwicklung des Gesichtes''*
and the splendid heliogravures of human embryos that Hoch-
stetter ' has published. Those who desire a comparison of human
development with that of animals I would refer to Hertwig's
**Handbuch"^ in which I have considered the development of the
external form in vertebrate embryos.

On account of the fundamental importance of His's '*Ana-
tomie menschlicher Embryonen,'' I here give a view of the

*W. His: Anatomie menschlicher Embryonen, Leipzig, 1880-1885.

'Gustav Retzius: Biologiscbe Untersuchungen, neue Folge xi, 1904.

'Keibel and Elze: Normentafel zur Entwicklungsgeschichte des Menschen,
Jena, 1908.

* Carl Rabl : Die Entwicklung des Gtesichtes, Leipzig, 1902.

*F. Hochstetter: Bilder der ausseren Korperform einiger menschlicher
Embryonen ans den beiden ersten Monaten der Entwicklung, Munich, 1907 (pub-
lished by F. Bruckmann).

*F. Keibel: Die Entwicklung der ausseren Korperformen der Wirbeltier-
embryonen, etc., Hertwig's Handbuch, 1906, vol. i, chap. 6 (published 1902).

59

HUMAN EMBRYOLOGY.

'g)'p%-o^'^

DEVELOPMENT OP HUMAN EMBRYO. 61

development of human embryos as shown in His's Normentafel,
the first fifteen figures, as in the original, being enlarged five
times, the remaining ones only two and a half times.

Fia. 34. n.—Tht embryo) of Hie'e Noraieiitsfel, from th« Normenlafel of Keibel ud Elu (Fig. 1, p. S)
X 2.B. Hia'anumbera are given in parentheses.

The individual embryos are lettered, His's numbers being
given in parentheses.

To this reproduction of His's Normentafel I append a
synoptic table from which it may be seen how His designated each
embryo, its size, and its age, as estimated by His.

62

HUMAN EMBRYOLOGY.

Fig. No.

His's designation.

a
b
c
d
e
S
Q
A

i

(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)

*(10)

'(11)
m(12)

n(18)
0(14)
3) (16)
fl(16)
r(17)
• (18)

«(1»)
«(20)
f(21)
10(22)
«(23)
y(2l)
«(25)

Embryo E (VII)

Embryo 8R (VI)

Embryo Lg (LXVIII).
Embr>o8ch (LXVI)...

Embryo M (IV)

Embryo Lr (LXVII) . .

Embryo a (III)

Embryo R (LVII)....

Embryo A (II)

Embryo Pr

Berlin anat collection. .

Ruge'8 collection

Embryo M (X)

Embryo Br (XXIX)..
Embryo Rg (LXXIV) .
Embryo 8i (XXXV) .
Embryo cn

Embryo 8chs(XLVI)...

Ruge'8 collection

Embryo Dr (XXXIV)
Embryo 8j (XXXVI)

Embryo XCI

Embrj'o Ltz

Embryo Zw

Embryo Wt (LXXVII)

Size in mm.

Source.

L.
L.
L.
L.
L.
L.

2.1

2.2

2.15

2.2

2.6

4.2

Nl. 4.0
Nl. 6.5
Nl. 7.5
Nl. 10.0
Nl. 9.1
Nl. 9.1
Nl. 10.5
Nl. 11.0
Nl. 11.5
Nl. 12.5
Nl. 13.7
L. 13.8
L. 13.6
L. 14.5
L. 15.5
L. 16.0
L. 17.5
L. 18.5
L. 23.0

Uterus

UteruB
Uterua

UteruB

Extra-uterine

Estimated ago in
days.

12-15

12-15

12-15

12-15

18-21

18-21
23

24-25

27-80

27-30

27-30

27-30

81-^

31-84

31-34

31-34

31-34

About 85

About 35

About 37-38

About 39-40

About 42-45

47-51

52-54
60

To avoid repetition I shall not proceed to describe His's
Normentafel, but will consider a series of embryos which, in my
opinion, present the best summary now available of the develop-
ment of the external form of the human body ; and in doing so
I shall have occasion to consider the embryos of the Normentafel
in their appropriate places. The so-called ^^^ membranes will
be described only in so far as they influence the form of the body.

Nothing need be added here concerning the youngest human
embryonic disks to what has already been said in the chapter on
* ^ The Youngest Human Ova and Embryos. ' ' The embryonic disk
of the Peters ovum had a length of 0.19 mm. ; whether it possessed
a very small primitive streak must remain doubtful. In Spee's
Von Herff ovum the disk had an oval outline and presented a
median groove lying between the dorsally convex lateral portions,
which were somewhat unequal in the transverse direction. This
groove is the primitive groove, and it may be supposed that the
primitive streak extends through the entire length of the
embryonic disk, since Spec says: ^'The entire anlage of the
embryonic disk is apparently only a portion of the actual primitive
streak region.''

DEVELOPJIENT OF HUMAN EMBRYO. 63

Close upon the embryome disk of Spee's Von Herff ovrnn fol-
lows that of the Frassi ovum. In the former the primitive streak
was at the height of its development, extending
as it did throughout the entire germ; in the Frassi
ovimi it is about half the length of the embryonic f

disk, and at its cranial end it shows the anlage of
a neurenteric canal, while at the caudal end, as
has been noted (p. 36), the anlage of a eloacal
membrane has appeared. In front of the primi-
tive streak there is a shallow medullary groove
bounded by low medullary folds. The entire em-
bryonic disk is slightly convex in the eraniocaudal
direction and from right to left, and it covers the -
yolk sack like a lid. ^"■*'

Following this embryo that
of Spee's Glaevecke ovum (Fig.
37) may be mentioned. The
actual embryo had a somewhat
"constricted pear-shaped" out-
line, and within tiiis the outline
of the biscuit-shaped medullary
plate was distinctly marked. Fio.3e.

The caudal end of the embryo F'"- « «") m.— The Fnni «nbiyo (Nor-

, , , , 1 II 1 meuurel of Kwbal and EIh. Fig. I. plate 1). Fig.

was bent Snarpiy centrally, al- 35 BhowBtb« embryo fraiiiabovauidFic.3errom

most at a right angle, and, xVV5'kf™o.^.i^"b/ESr^^' ^™'

consequently, when looked at

from above, appears greatly foreshortened. SHglitly cranial to

this downwardly bent portion there is a somewhat circular swell-
ing, that in position corresponds to Hen-
sen's node and surrounds, like a low wall,
a roundish triangular opening, the neu-
renteric canal; behind this swelling is the
primitive groove, resting upon the primitive
streak. Anteriorly the primitive streak is
embraced by the medullary folds. For the
measurements of the embryo consult Chap.
IV, p. 39.

Next to this embryo comes embryo 1 of
His's Normentafel.

This embryo was obtained from an o\iim that

; measured in the fresh condition 81 X 5i mm. and was

completely siiiTonnded by villi. The len^h of the

Fro. 37. — Graf Spee's Glae- embryo, including the belly stalk, was 2.6 mm., and

SiSS./K"i..'LTES ""■<'°' "" •»"? ■'•"■ ™ 2.> »■»■ The yolk »ck
Fig. II, plate 2.) was somewhat flattened and measured 2.3X1-^ nun.

The embryo rested upon the yolk sack for about 2 mm. of its
length and was enclosed in an amnion which also surrounded the

61 HUMAN EMBRYOLOGY.

upper surface of the belly stalk. In the embryo itself, the section-
ing of which was unsuccessful, the medullary folds and medullary
groove could be recognized, and laterally from the medullary folds
at the anterior extremity the anlage of the heart was visible.

I place next the embryo Kib. of the Normentafel of Keibel
and Elze, Figs. Hid and Ilia. The ovum which contained the
embryo was obtained by a laparotomy and both it and the embryo
may be regarded as quite normal. The embryo had five to six pairs
of primitive somites. The vertex bend had already begun to
form, otherwise the embryo lies flat on the yolk sack; it has no
dorsal bend. Fig. 38 shows it from the dorsal surface, and, the
amnion being cut away, it is seen to be attached to the chorion, a
small portion of which is represented, by a
short belly stalk. To the right and left of
the cut edges of the amnion the yolk sack
projects beyond the
embryonic struct-
ures. Both the cra-
nia) and caudal ends
of the embryo are
separated from the
yolk sack, but the
middle portion is
jonneDufai of Keibd Still Spread out dat.
^^- The medullary

groove is widely
open, but rather deep. Caudally the medullary folds embrace the
dorsal opening of the neurenteric canal and the cranial end of the
primitive streak, which immediately bends downward so that it
cannot be perceived in its entire extent; indeed, it lias already
undergone much retrogression. The well-marked medullary
anlage shows the vertex bend, so that its cranial end cannot be
seen in a dorsal view. The brain part of the medullary anlage
shows a separation into three portions, the most caudal of which
extends to about the fourth pair of primitive somites and then
passes without any marked boundarj' into the spinal cord. I may
here note that by far the greater part of the dorsal region of this
embryo belongs to the later head region. The boundary between
the head and trunk regions passes through the fourth primitive
somite. The most anterior somite of the neck region is first
differentiated.

Fig. 39 shows the embryo from in front. The amnion has
again been removed; ventrally the relatively large yolk sack is
seen. Of the embrjonic anlage only the ventrally bent portion,
as far back as about the vertex bend, can be seen; but it may be
observed that the most anterior portion of tlie brain anlage is

DEVELOPMENT OF HUMAN EMBRYO. 65

relatively greatly developed. The medullary groove terminates
a little behind the cranial end of the medullary aniage, so that the
latter shows anteriorly a transverse ridge. Nothing is yet to be
seen of the optic pits, the forerunners of the optic vesicles.

Regarding the measurements of this embryo Kromer makes the following
statements: "The greatest length of the embryonic aniage from the anterior
amniotic border of the head cap to the chorionic end of the belly stalk was 1.95 mm. ;
the length of the embryo, without the belly stalk, from head to tail was 1.8 mm. ; the
greatest breadth of the yolk sack was barely 1.2 mm. ; the breadth of the embryonic
disk at the junctioti of the amnion and yolk sack (measured in an anterior view)
was 0.9 mm." The size of the yolk sack was 1.1 mm. iu height, 1.1 mm. in breadth,
and 1.5 mm. in length.

After this embryo, that represented in Fig. 2 of His's Nor-
mentafel may follow, although on account of its possessing a
dorsal flexure I am somewhat in doubt if it is normal in form.
Its greatest length was 2.2 mm. The greatest di-
ameter of the somewhat collapsed yolk sack was 1.9
mm.; and the embryo rests upon it in such a way
that anteriorly the head end, for a distance of 0.4
mm., and posteriorly the caudal end, for a distance
of 0.5 mm., project beyond the yolk sack navel, which
is 1.3 mm. in length.

The body of the embryo shows the middle of the
dorsal surface somewhat depressed and the head
and tail ends are somewhat bent downwards. The
margins of the medullary plate are still wide
apart, and a number of primitive somites, how many
could not be exactly determined, were formed. The
aniage of the heart was still paired, and upon the
surface of the yolk sack there were numerous wart-
like elevations (anlagen of blood-vessels). fiq.w.— The

The Bulle embryo of Kollmann (Fig. 40) may oJ^Koi'^^^n"
well come in here or even after the embryo Klb. -20- (Fromti*
Both the head and tail ends project beyond the yolk Kei™'^*EiM,
sack, which communicates widely with the intestine. Fig. iv, plw s.)
BO that one cannot yet speak of a yolk stalk. The
yolk sack has been cut away, except for the part by which it is
continuous with the embryo; and similarly the amnion has been
cat away not far from its root; under the caudal end of the embryo
is to be seen the belly stalk. The figure shows the embryo from
behind and from the right, so that the heart swelling is hidden.
The brain portion of the medullary canal, in which the segments
of the brain can be seen, is still open, and the caudal end of the
canal is also open, although this cannot be perceived from the
figure. If we reckon three of the fourteen primitive somites as
belonging to the head and eight to the neck re^on, there still

66 HUMAN EMBRYOLOGY.

remain three as representing the tliorax ; in the relatively small
caudal end of the embryo almost all the segments of the trunk
and tail must still be represented. In the region of the sixth to
the fourteenth somites the dorsal surface of the embryo is slightly
depressed. Kollmann says: "In the region of the sixth primitive
somite the flexure of the dorsal region, which later becomes so
striking, is noticeable." I cannot recognize in the figures of the
embryo a flexure in the region of the sixth somite, and in any
case the sixth segment belongs to the neck region. That a dorsal
flexure occurs at this stage or later in normal human embryos I
regard as disproved, and in this Spee^ is in agreement with me.
In 1905 ^ I had come to the conclusion that even if a dorsal flexure
normally occurs in human embryos it can only be at a stage
of development in which six or at the most twelve primitive
somites are present. I do not, however, regard the evidence
of its occurrence at this stage as sufficiently based upon the
embryo that Eternod " has had modelled by Ziegler and upon an
embryo with seven ])airs of
primitive somites belonging
to Graf Spee.'"

It is a question whether
in this and other cases one
has not to deal with a de-
formity produced by swelling.
(For further consideration of
this matter see the Normen-
tafel of Keibel and Elze, pp.
22-23.)

The greatest length of
the embryo, measured after it
had been preserved in alco-
hol, was 2.36 mm.
The embryo Pfannenstiel III (Figs. 41 and 42), figured in
Keibel and Elze's Normentafel, has the same number of primitive
somites as the Bulle embryo of Kollmann, yet it is more de-
veloped. It was obtained from a hysterectomy and was modelled
by Elze. The medullary tube is open in the brain region as well as
caudally; but, in addition to the vertex bend, present in the embryo
Klb., a nape bend has appeared ; there is no indication of the dorsal

'Scliwalbp's Jahresbericht, Jena, 1906, neue Folge, toI. xi, 2 Abt., p. 225
(literaltire of 1905).

'Keibel: Zur Embrjologie des Menschen, der AfEen und der Halbaffen,
Verh. Anat. Ges. (Genf), 1305; also in C. R. Soc. dea Anatomistes, 1905.

* Compare A. C. F. Eternod : II y a un canal notochordal dans I'embryon
humajn, Anat. Anz., vol. svi, 1899.

'"Graf Spee: Mitteilungen iiber den Verein selileswig-liolsteiniselier Aerzte,
vol. xi, article 8, 1887.

42— T

X20.

Fig-.

(From Ih
Vr unil Vv

Nomw

nUfel of Keibel sod Elu,

DEVELOPMENT OP HUMAN EMBRYO. 67

flexure. The optic pits were distinct and the auditory epithelium
was slightly depressed. The greatest length of the embryo meas-
ured 2.6 mm.

The flexure which I have termed the nape bend was very
striking in this embryo. If it be normal, it is very doubtful if the
nape bend that is found in later stages is comparable with it,
and if it does not later disappear before the well-known nape bend
of later stages develops. Older embryos of mammals and also of
man, such as embryo 3 of His's Normentafel, still lack a nape bend,
as does also an orang-outang corresponding to this last embryo."

At this point a great gap unfortunately occurs ifi our aeries
of human embryos, so that a settlement of the question is at
present impossible. The embryo shown in Pig, VI of the Normen-
tafel of Keibel and Elze had already twenty-three pairs of
primitive somites ; in addition, our ideas as to its external form
are based upon a not very successful model, whose head region
presents a very improbable form. I shall not, therefore, give a
figure of the embryo here, but merely describe it briefly. It shows
a well-marked vertex bend, but no distinct nape bend; and it is
spirally coiled, so that its tail
end comes to lie to the right
of the very large belly stalk.
The medullary tube is still
open at its caudal end. The
heart swelling lies entirely
in the amniotic cavity, and
through its thin wall the heart
must certainly have been shad-
owed. Three branchial arches
and as many branchial furrows
were recognizable, and dorsal
to the second furrow there was
the already greatly narrowed
opening of the ear vesicle, j^^
The extremities have not yet
formed.

Embryos 3, 4, and 6 of His's Normentafel, Fig. 34, c (3),
d. (4), and ^ (6) I regard as abnormal; c (3) and d (4) show the
much discussed dorsal flexure and / (6) seems to me for other
reasons to be excluded from the series.

The embryo shown in Fig. 34, e (5), seems to me more worthy
of confidence; and I repeat it here, more highly magnified, as
Fig. 43. It came from an ovum which measured 7.5-8 mm. in
diameter and was completely surrounded with villi. The amnion

"See F. Keibel: in Selenka's HenschenaiTen, 9 Lieferung, 1906.

68 HUMAN EMBRYOLOGY.

lies close to the embryo and does not yet entirely enclose the heart.
The body of the embryo is bent upon itself anteriorly and at the
same time twisted about its axis so that the head end is turned
toward the left and the pelvic end toward the right. The dorsal
curvature is very regular, and the nape prominence is not yet
pronounced. The anterior portion of the head is bent ven-
trally to such an extent that the vertex is formed by the mid-
brain. Behind the anterior part of the head there is a deep
depression, which indicates the entrance of the oral sinus and is
continued dorsally in the orbitonasal groove. Behind the mouth
cleft is a broad mandibular process, separated by a groove from the
second visceral arch; and the posterior boundary of this second
arch can also be made out. The study of the entire embryo
revealed no clear picture of the third and fourth arches, although
their presence was quite evident in sections. The anlage of the
heart projected from the ventral surface of the body as a broad
transverse swelling; its prolongation on the right side extends
forward as the aortic bulb to the edge of the mandibular process.
To the atrial portion of the heart belongs an outpouching which
is seen ventral to the hinder portion of the head, on the lateral
wall. Immediately behind the heart the umbilical vesicle (yolk
sack) projects from the umbilicus, which has the form of a longi-
tudinal cleft; the yolk sack was somewhat sunken in and was
pyriform in shape.

The pelvic end of the body is curved forward in a hook-like
manner and on account of the twisting of the embyro cannot be
seen from the left side. In the posterior half of the trunk one
sees four parallel longitudinal ridges, two of which, the medullary
and somitic ridges, belong to the axial zone, while the other two,
the WolflSan and marginal ridges, belong to the parietal zone. No
traces of the extremities are yet visible. According to His's
estimate there were thirty-five pairs of primitive somites. His
gives the following measurements:

Greatest length in a straight line 2.6 mm.

From vertex to behind the mandibular process 0.7 mm.

From vertex to behind the heart 1.4 mm.

Height of yolk sack where it projects from umbilicus 0.6 mm.

Maximal height of yolk sack 1.7 mm.

Length of yolk sack 2.6 mm.

Length of the posterior portion of the body, measured

from the point of emergence of the yolk sack 0.6 mm.

The first embryo of Hochstetter's series (Fig. 44), which
belongs to Professor Fischel of Prague, presents a very great
advance in development. As the figure shows, it is not only very
greatly curved upon itself, but it is also strongly twisted spiraUy.
In the head one sees the primary optic vesicles and on the first

DEVELOPMENT OP HUMAN EMBRYO. 69

branchial arch an early indioation of the maxillarj- process. Both
upper and lower extremities are recognizable, the former being
plate-iike. The definitive nape bend is strongly developed. The
greatest length of the embryo was 4.02 mm. ; it was obtained as an
abortion.

The embryo which I would place next in tlie series is embryo
G 31 of the Anatomical-biological Institute of Berlin (Fig. 45)
{Fig. VIII of the Normentafel of Keibel and Elze) ; it stands close
to embryo 7 (Fig. 34, g) of His's Normentafel, Its greatest length
is the nape-breech length (nape line) and is 4.9 mm.; the vertex-
breech length is 4.7 mm. It is rather strongly curved upon itself,
but more regularly than the preceding embryo ; the nape bend is
strongly marked, and the spiral twisting is still quite distinct.
The tail lies to the right. The upper extremities are plate-like in
form, the lower ones ridge-like. The anterior end of the head
shows in the middle line a slight depression, and the anlagen of the
eyes show through the integument. The region of the later sinus
cervicalis is still but little depressed, so that the third and fourth
branchial arches are quite
easily seen. The atrial and
ventricular portions of the
heart can be distinguished
through the thin wall of the
pericardial cavity.

A few words may be said
concerning embryo 7 of His's
Normentafel(Fig.34,5). This
embr}'o has reached the high-
est degree of curvature that
has yet been observed in the
human embryo. The length
from the forehead to the tip
of the coccyx following the
curvature was 13.7 mm.; the
straight line from the nape
prominence to the twelfth
thoracic segment, the nape
line (NL), was 4 mm. in „Jh™te "r^."U™n"K.riK^J"^'.

length. The tail end was «hli<^l«r EB.bry™a. Munich, F. B™ckm«ui.)

curved forward to the level

of the ventricle of the heart and lay upon the left side of this.
In the eur^'e which is formed by the embryo from the forehead
to the tip of the coccyx there are four regions where the bend-
ing is stronger than elsewhere: (1) the region of the mid-brain;
(2) the nape prominence; (3) the boundary between the neck
and thoracic regions; and (4) the boundary between the abdom-

70 HUMAN EMBRYOLOGY.

inal and pelvic regions. The plane of symmetry of the embrj'o
is warped and is twisted in such a way that the head looks
to the right and pelvic end to the left. The upper extremities
are plate-like, the lower ridge-like.

At the head end the shape of the
cerebral hemispheres, tlie tween-brain,
mid-brain, hind-brain, and after-brain,
is plainly recognizable, and the bound-
aries of the fourth ventricle are
sharj)Iy defined. In a view from the
dorsal surface tlie lateral walls of the
' fourth ventricle show a series of regu-

lar and bilaterally symmetrical trans-
verse folds (neuromeres). The optic
vesicles form on each side a circular
circumscribed projection measuring
0.35 mm. in diameter, and tlie audi-

Fio. 45. — The embryo (1 31 nt . . , ■ i ^ .

the Aoatomioi-bioiogici inMiiute in tory vesicles are very evident as oval
Ktib^i*.nd'Ei»^FS.'Y°iii?Xi"'u*)''' structures lying at the level of tlie sec-
ond visceral groove. In addition to
tlie moderately developed maxillary and mandibular processes the
lateral wall of the bead shows on each side three \isceral arches,
the fourth of which is still fully exposed. The distance from the
anterior border of tlie ma-xillar}- process to the fourth branchial
groove was 1.4 mm,; a line drawn through the ventral ends of all
four arches was almost straight and
cut the fore-brain some distance in
front of the optic vesicles. The an-
terior borders of tliese were about
0.55 mm. from the anterior pole of
the fore-brain, so that the prominence
of the fore-brain characteristic of
human embryos in all later stages of
development is already present. Im-
mediately behind the ends of the vis-
ceral arches is the heart, the three
portions of which are plainly visible
when the embryo is examined from

both sides, witli this difference, how- fig. ■lo. — Embryo 112 ot Keib«i'*
ever, that the atrial swelling is more Cf'Keib^r.nj Ei'ie! ViT'ixtr^^Ttt'oj''
distinct on the left side and the swell-
ing of the aortic bulb on the right side. No deep cleft yet separates
the swelling produced by the aortic bulb from the facial surface
of the head. The visceral region of the body lying behind the
heart shows on the right side a distinct Wolffian ridge and the
transition border of the amnion; on the left side no cliaracteristic
elevations are visible.

DEVELOPMENT OP HUMAN EMBRYO. 71

Near I'ig. 8 of His's Normantafel (Fig. 34, h) stands the
embryo shown in Fig. 46. Jt was obtained as an artificial abor-
tion. It shows the vertex and nape prominences and is not only
strongly curved on itself but is also spirally twisted. The olfac-
tory area is beginning to show a better delimitation dorsaily and
laterally, and the maxillary process can be seen in a profile view.
In the region of the sinus cervicalis which is still widely open, the
third and fourth branchial arches are plainly exposed; the heart
swelling is very prominent and the atrial and ventricular portions
of the heart are recognizable. The liver swelling la still but poorly
developed, and the tail is curved in between the heart swelling and
the belly stalk. Dorsal
to the primitive somites
ore sees O. Schultze's "
division of the sclero-
tomes. The embryo had
thirty-six pairs of so-
mites.

Between embryos 8
and 9 of His's Nor-
mantafel (Fig. 34, ft
and i) there is a rather
wide interval, into wliich
the erabrvos shown in
Fig. X and Fig. XI of
the KeJbel-Elze Normen-
tafel fit. The erabrj-o
shown in Figs. XII and
XIr corresponds fairly
well with the Braus- em-
bryo shown in Figs. 2

and 3 of Hochstetter'S Fio. 47. — The Brsm embryo. XIO. (From Hoehitcller:

series. For explanation m^"i,,''" b"S".>.^) '^"''™ ™°"'''"*" Embr^-ooe,.,
of the figure of this,

shown in Fig. 47, a few words will sufiice. The olfactory area is
beginning to be delimited more sharply dorsaily and caudally; the
first and second branchial arches have now become relatively targe
and have begun to be further modified; the triangular area caudal
to them, in which the third and fourtli arches are situated, is
slightly depressed, forming the sinus cervicalis ; the upper extremi-
ties have passed from tlie plate-like into the stump-tike stage.

Following closely upon this embryo comes embryo 9 of His's
Normentafel (Fig. 34, 0- In it the nape bend is more strongly
marked, so that the head is much more bent down upon the heart;

"0. Schultze: Ueber etnbryonale und bleibende Segment ienmg, Verb, Anat.
Oes., 1896, pp. 87-93.

72 HUMAN EMBRYOLOGY.

the distinctly circumscribed olfactory pit rests upon the heart.
The tips of the anterior extremities have become bent ventrally,
and the roots of the extremities are correspondingly angled. In
the trunk one sees three tumor-like projections, of which the two
situated more cranially and ventrally are produced by the ven-
tricular and atrial portions of the heart, while that lying more
caudally and dorsally is formed by the liver. The embryo shows
a very distinct external tail. The external configuration of the
head is principally determined by tlie subdivisions of the brain,
whose shapes are clearly recognizable through their thin covering.
At the base of the fore-brain is the olfactory pit, and a slight dis-

tance in front of this is the eye with the lens groove. The small-
ness of the eye oomi)ared with the great development of the fore-
brain is characteristic. A prominence behind the eye marks the
position of the ganglion of the trigeminus; it lies in the angle be-
tween the raid-brain and hind-brain. At the level of the second
visceral groove the auditory vesicle, together with the ganglion
acnsticum lying in front of it. forms a slight elevation. Elevations
are beginning to appear on the mandibular process and hyoid arch ;
the third and fourth branchial grooves lie at the bottom of a
triangular depression, which will become the sinus cervicalis.

Embryo 10 of His's Normentafel is comparatively large for
the degree of development it presents; it resembles the preceding
embryo, and was taken from a uterus.

DEVELOPMENT OF HUMAN EMBRYO. 73

74 HU5IAN EMBRTpLOGT.

Embryo XIV of the Keibel-Etze Normentafel (Fig. 48) is not
quite so large, but is more developed. This is shown especially
by the condition of the extremities and of the sinus cervicalis.
Behind the dorsal part of the hyoid aroh one may perceive the
entrance into the glossopharyngeal organ (the second branchial
groove organ). In the upper extremities the band plates are dis-
tinct Forty trunk somites were counted, and the last six of

Fio.62.— The embryo P.I of Hoehstetter. X 10. (From Iho Normcnufcl ol Kcibel and Elie, Fia. XK.
plsle 45.)

these were beginning to be transformed into a tail filament. The
embryo was obtained from an artificial abortion.

The embryo to which we now come may be considered not
only from the left side (Fig. 49) hut also from the dorsal (Fig.
50) and ventral (t^g. 51) surfaces. It is the Hoehstetter embrj'O
Ma. 3, Fig. XVII of the Keibel-Elze Normentafel and Figs. 7,"8,
and 9 of Hochstetter's series. The trunk region has again begun
to elongate. The spiral twisting is evident only to a slight extent
in the tail region, the tail lying to the left of the belly stalk. The
nape bend is almost a right angle; the cerebral hemispheres are

DEVELOPMENT OP HITMAN EMBRYO. 75

recognizable externally; and the cerebellum shows out plainly,
especially in the ventral view (Fig. 51). The axes of the upper
limbs are almost parallel to the dorsal line; the hand plates are
almost circular; the elbows show especially distinctly in the dorsal
view (Fig. 50); and in the same view one may perceive, on the
surface of the upper limb which looks towards the trunk, a small
tubercle. In the lower limb the foot plates are marked off. Dorsal
to the row of primitive somites one can clearly distinguish
Schultze's segmentation of the sclerotomes. The maxillary pro-
cesses have come into relation with the median nasal process, the
openings of the nasal pits look towards the wall of the pericardium
and are no longer to be seen
from the side, especially from
the left. A distinct sculpturing
is present on the mandibular
process and especially on the
hyoid arch. The entrance into
the sinus cervicalis is still vis-
ible as a small triangular hole.

In part somewhat more and
in part less developed tlian this
are embryos 11, 12, and 13 of
His's Normentafel (B'ig. 34, I,
m, and n) ; that shown in Fig.
11 (I) was taken directly from
the uterus. In that shown in
Fig. 12 (m) a small nape fur-
row has formed beneath the
strong nape prominence and tlie
position of the upper extremi-
ties does not seem normal. In ^">- M.— The embryo Clir. a of Hochstetter.
,, , , . T7,- -,« / , ■■ >;5. (From Ihe Normentafel ol Keibel and Elie.

that shown m rig. 1^ («) tlie Fig. xx. pist* ei.)
body is relatively slender and a
heart swelling cannot be made out.

The body of Hochstetter's embryo P. 1 (Fig. 52) (No. 10 of
Hochstetter's series, Fig. XIX of the Normentafel of Keibel and
Elze) is already rather elongated. The elbows have moved out
from the body and the forearm makes an acute angle with the
dorsal line. The fingers are beginning to become distinct on the
hand plates, and tlje foot plates have become circular. Close to
this embryo come those shown in Figs. 14, 15, 16, and 17 of His's
Normentafel (P^ig. 34, o, p, q, and r) ; in Figs. 15, 16, and 17 the
thumbs are distinctly recognizable.

In the lower limbs of Figs. 18, 19, and 20 of His's Normentafel
(Fig. 34, 5, t, u, and v) the aniagen of the toes can be seen. The
head is gradually bending to the erect position, and in correspond-

HUMAN EMBBTOLOQT.

DEVELOPMENT OP HUMAN EMBRYO. 77

ence with this the neck is forming; the formation of the external
ear is also making progress. These stages may be represented
here by Hochstetter's embryo Chr. 2 (Fig. 53, No. 15 of Hochstet-
ter's series, Fig. XX of the Keibel-Elze Normentafel), Eabl's em-
bryo C (Figs. 54, 55, and 56, Nos. 16, 17, and 18 of Hochstet-
ter's series) and the embryo No. 302 of Robert Meyer's collection
(Fig. 57, Fig. XXI of the Normentafel of Keibel and Elze).

In the embryo Chr. 2 the nape bend is somewhat more than
a right angle. The mouth lies in close contact with the peri-
cardium, and the nose has become free from it. The folds of
the pinna, the tragus and the antitragus, are formed; the concha
is widely open and flat. Behind the nape prominence the contour
of the back shows a distinct depression. The fingers have become
quite pronounced and the toes are just indicated, but the position
of the great toe is already to be recognized. The elbows and
knees are evident, and the angle that the axis of the forearm
makes with the dorsal line is almost a right angle.

Slightly further developed than this is Rabl's embryo C
(Figs. 54, 55, and 56). The nose is more marked off, the eyelids
are further advanced, and so also the ear. The finger-tips are
distinctly projecting beyond the border of the hand plate. In
the ventral view one may note the position of the eyes and of the
limbs. Between the foot plates may be seen the physiological
umbilical hernia. The tail has become transformed into a coccy-
geal tubercle. In the dorsal view the sharp slope of the caudal
portion of the trunk is striking.

The embryo 302 of Robert Meyer's collection (Fig. 57) shows
a distinct depression between the root of the nose and the fore-
head. The pinna, tragus, and antitragus are evident; and while
the concha is still widely open it shows a tendency to deepen.
Early indications of the eyelids are to be seen. The nape flexure
is still very evident, but it forms an obtuse angle, and the depres-
sion of the dorsal line just below it is less marked. The nose and
mouth have both separated from contact with the pericardium ; the
mouth is slightly open and the mandible lies close upon the breast.
The shoulder is distinctly marked off from the body, the upper
arm makes an angle with the forearm, and the elbow projects
strongly. The hand plate is beginning to turn ventrally, and the
finger anlagen are very distinct; their tips are becoming free and
the thumb is strongly abducted. In the lower limb the knee is
very distinct and anlagen of the toes are appearing on the foot
plate. The dorsum of the foot is not yet marked off from the crus.

When we pass from embryo 21 (Fig. 34, v) to embryo 22 (Fig.
34, w) of His's Normentafel, we are passing from the embryonic
to the fetal stage. The profile of the latter embryo already shows
clearly a nose, upper lip, lower lip, and chin ; and the neck is also

n

78 HTI^LAN EMBRYOLOGY.

present The eyelids are formed, and above the eyes there is a
distinct supra-orbital swelling. The upper limb, in which tho
fingers have become distinct, has increased in length considerably
and shows a distinct division into upper arm, forearm, and hand.
The shoulder has formed, and the characteristic position of Uie
arms is worthy of note. In the lower limb the foot, crus, and thigh
can be distinguished. The aniagen of the toes are not yet sepa-
rated from one another, but that of the great toe ia especially well
marked. The nape promi-
nence and nape depression
are much reduced, and the
coccygeal tubercle still ap-
pears as a short stumpy tail.
Witli the three remain-
ing stages of His's Normen-
tafel, Figs. 23, 24, and 25
(Fig. 34, X, y, and z) the
transition from embryo to
fetus has been accomplished.
In Fig. 34, X, one sees the
toes separated from each
oUier, and tlie great toe has
a characteristic abducted po-
sitiou, recalling the position
of the thumb in the corre-
sponding stage in the devel-
opment of the hand. In Fig.
34, y, the foot is better
formed ; the legs have under-
gone a twisting so that the
knee looks more upwards
and tlie foot more down-
wards. B^g. 34,2, still shows

Fio. S7 — Embryo 302 ol Robirt Meyer. Berlin. a Slight UapO prOmiuenCe
XXI. pbT64'.^ Normeolafel of Keibel .«! El„. Fi,. ^^^ ^ ^,^^^ shallOW Uape de-
pression. The small crea-
ture shows a distinctly human character in its features. Some ad-
ditional figures may complete the story.

The embryo shown from in front in Fig. 58 corresponds some-
what to Fig. 22 {Fig. 34, w) of His's Normentafel. The position
of the eyes, the broad nose, and the position of the limbs may be
noted.

A' fetus measuring 25 mm. in its greatest length js shown from
the left side and from the ventral aspect in Figs. 59 and 60, re-
produced from the Normentafel of Keibel and Elze. It may be
regarded as standing between Figs. 24 and 25 (Fig. 34, y and z)

DEVELOPMENT OP HUMAN EMBRYO. 79

of His's Normentafel. Again I would call attention to the position
of the limbs. In Fig. 59 we see touch pads on the sole of the
right foot. At the summit of the coccygeal tubercle there is a
small knob, as in all well-preserved embryos of this stage, and it
is also seen in the ventral view (Fig. 60), in which the physiological
umbilical hernia is indicated by the coils of the intestine showing
through the wall of the cord.

We may now again pass in review the stages which the human
embryo must traverse in order to acquire
its human form. The earliest known
embryos are flat, shield-like plates which
rest upon tlie yolk sack. At a certain
stage a primitive streak extends through-
out the entire length of the shield; in
front of the primitive streak the embryo
is formed, and it grows at the expense of
the streak, which retrogresses in a cranio-
caudal direction. The streak is thus con-
verted into a growth zone, which may be
termed at first the trunk bud and later
the tail bud. To correctly understand
these processes of development we must
bear in mind the extent to wliich the head
region predominates in young embryos.

Beturning again to tlie primitive
streak, during its modification its caudal
end becomes bent ventrally; tlie cloacal
membrane had previously formed in this
caudal region, and it now comes to lie
on the ventral surface. This bending
process is associated with the constric-
tion of the embryo from the yolk sack ; f,o. bs.— buiiu. embryo, laa.
eranially and eaudally, from the right
and from the left, the boundary grooves
cut inwards and soon convert the yolk
sack into a stalked vesicle; in the meantime the dorsal portion of
the embryo grows more rapidly than the ventral, a condition
caused by the accelerated growth of the medullary anlage. Be-
fore the medullary plate is converted into a tube the brain, with
its principal subdivisions, becomes distinct at the anterior end,
and the optic pits are also formed. By the rapid growth of the
brain portion, while the medullary tube is still open, there is
produced a bending down of its cranial portion (the vertex bend)
and, if the Pfannenstiel embryo III {Figs. 41 and 42) is to be
regarded as normal, also the more caudal nape bend. It has
been already pointed out, however, on pp. G6 and 67, that a diffi-

80 HTIMAN EMBRYOLOGY.

culty exists in this particular. Embryos that are properly be-
lieved to be older do not show the nape bend distinctly, and
these agree with the embryos of other mammals, especially
with that of the orang-outang which I described in. 1906. There
are two possibilities : either the nape bend of the embryo shown
in Figs. 41 and 42 was an abnormality; or it is a primary nape
bend that normally disappears, the long known nape bend later
appearing independently of it. On account of the lack of the
necessary stages this question cannot be decided at present; but
in any event the entire embryo soon becomes curved on account of
the much greater growth of the dorsal surface, and coils itself
in a spiral. The spiral turns sometimes to the right and some-
times to the left. While these developmental processes are taking

sntslel oT Ktabti ftod Elie, Figa.

place there has formed from the tail bud a small but unquestion-
able external tail. In these stages also the head region still pre-
dominates to an extraordinary degree, but the embryo no longer
consists, as in the stages of the early primitive somites, only of the
future head, so to speak. The extensive coiling toward the ventral
surface is followed by a very gradual uncoiling; first the trunk
straightens out and the nape bend slowly becomes obliterated.
These processes are accompanied, perhaps determined, by a rapid
growth of the ventrally situated organs, especially of the heart
and liver, which produce on the surface of the body the heart and
liver prominences. The Wolffian bodies do not play a very im-
portant part in this respect in man. With the straightening out
of the nape bend opportunity is afforded for the formation of
the neck. Originally the face lies closely upon the heart promi-
nence and the ventral portion of the neck is entirely wanting,
"While its lateral parts are occupied by the branchial or visceral

DEVELOPMENT OP HUilAN EMBRYO. 81

arches. The transformation of these interesting structures will
be thoroughly described in other places; here the following may
suflSce. The third and fourth arches — quite transitorily there is
also recognizable the aniage of a fifth — remain small in comparison
with the first and second, the mandibular and hyoid arches, and
consequently the region in which they occur becomes depressed,
forming the sinus cervicalis, which becomes covered in by the
second or hyoid arch and its opercular process. In the region of
the first branchial groove there are formed on the mandibular and
hyoid arches a number of elevations and folds from which the ex-
ternal ear is formed; its development will be considered in detail
with the sense organs.

In determining the form of the head the brain is at first
almost the controlling organ, and its various parts can be dis-
tinguished until relatively late stages through the thin walls of
the head. Gradually the mesenchyme increases in the walls, and,
above all, the face begins to develop in the service of the principal
sense-organs and of the respiratory and digestive tracts; its
formation will be considered later on.

The ventral wall of the trunk is at first very thin, and the
heart with its various parts, the liver, and other viscera may be
seen through it. From the right and left the anlagen of the
skeleton and the musculature grow into the walls; inhibitions of
this growth may occur and produce ectopia cordis and fissura
stemi, which depend upon disturbances of this process in the
thoracic region. A portion of the intestine normally projects like
a hernia into the umbilical cord, in association with the outward
growth of the abdominal walls; thus the hernia funiculi umbili-
calis physiologica is produced. Normally this hernia disappears
with the further formation of the abdominal walls, but occasionally
it may persist as an inhibition structure.

On the ventral wall of the body the region from the umbilicus
to the end of the trunk is the original primitive streak territory.
That portion of the streak which was originally, before it became
bent ventrally, the caudal portion, but which is now directed
cranially, becomes encroached upon by the developing skeletal
and muscle anlagen of the trunk. If inhibitions occur in this
region ectopia vesicae and pelvic clefts may be produced, and
epispadias also belongs in this category. The openings of the
urogenital sinus and the anus and the intervening perineum arise
in the territory of the portion of the cloacal membrane which per-
sists after the formation of the abdominal wall below the umbilicus.
For an account of these developmental processes reference may
be had to the chapter on the urogenital apparatus.

That a tail occurs in the human embryo has already been
noted; embryos of 4^12 mm. NL. have a typical external tail, in

Vol. I.— 6

82 HUMAN EMBRYOLOGY.

-which a caudal gut occurs and which possesses more segments
and spinal ganglia than persist. This external tail (cauda aperta)
becomes transformed in its distal portion into a tail filament,
which is knob-like in the human embryo and is later cast off,
while the remaining portions become overgrown by the neighbor-
ing parts and so disappear beneath the surface; in this situation
remains of it may persist, forming what is termed the internal
tail (Braun, 1882) or cauda occulta (Rodenacker, 1898).^^

If one now glances at the body as a whole, one can hardly
fail to be struck by the fact that the cranial portion is much more
fully developed, up to relatively later stages, than the caudal
portion ; this is shown very clearly by the dorsal views of embryos,
and I would call attention, in this connection, to Figs. 51 and 55.

The extremities first appear as ridges which later are con-
verted into plates, becoming more sharply defined cranially and
caudally. The portion which is first formed corresponds essen-
tially to the anlage of the hand or foot ; gradually the anlagen of
the forearm and crus, and then those of the upper arm and thigh,
grow out from the body. The further differentiation of the ex-
tremities, as well as tliat of the face and head, will now be con-
sidered more thoroughly, and for this purpose good figures are
much more important than extensive descriptions.

The figures showing the development of the face in the first
stages of its formation are rather few in number, since the pro-
cesses cannot be well observed in the human embryo without dis-
section, and dissection prevents the obtaining of a continuous
series of sections. I shall start with a stage that Rabl estimates
at nineteen to twenty days ; according to the estimate of Bryce and
Teacher (see pp. 26 and 27) it would be considerably older. It
corresponds essentially to Fig. VI of the Normentafel of Keibel
and Elze and to embryo 5 (Fig. 34, e) of the His Normentafel.
Fig. 61 shows a profile view of it. Three branchial arches are
recognizable ; on the first the maxillary process cannot be seen in
this view, although it is present, as may be seen from the front
view (Fig. 62). The optic vesicles, which are directed laterally,
show through the wall of the head, and over the second arch are the
auditory vesicles, not yet quite closed. In the front view (Fig. 62)
one looks into the pentagonal oral sinus ; it is bounded above by
the frontal process, laterally and above by the maxillary processes,
and below by the mandibular processes. Much more developed is
the face that I reproduce (also from Rabl) in Fig. 63. It is from
an embryo which measured 8.3 mm. in the preserved condition and
belonged, according to Rabl's estimate, to the fourth or perhaps the
beginning of the fifth week. It corresponds fairly well with Fig. 11

M

Compare Keibel in Hertwi^s Handbuch, vol. i, part 2, p. 151.

DEVELOPMENT OP HUMAN EMBRYO. 83

(Fig. 34, 0 of His's Normentafel and to Fig. XIV of those of
Keibel and Elze. The pentagonal opening of the oral sinus has
transformed into a broad
mouth-cleft, whose lower
border shows a notch between
the two adjacent ends of the
mandibular processes. The
nasal pits are distinct; they
are deeper dorsaliy and are
flattened out ventrally. One
may also speak of the two
nasal processes, that is to say,
the ridges which bound the
nasal pits laterally and medi-
ally. The portion of the
frontal process between the
medial nasal processes is still Fro«. et >«■ 62. — H«d end of an embryo «.

VPrv hrnnH /o» and from the left. The embryo oorrMpoocl* lUMn.

VKl^ UlUau. li«]Iy to embryo M of His (here FiB. 43). X 20. (From

The advance that is to be <-'■ ^•'''' ^'' Enlwicklung«ge»cbichl« dei Cesiohtes.

seen m Fig. 64 (a.a:am from

Eabl) is quite marked. The figure represents the face of an
embryo that corresponds to Fig. 14 (Fig. 34, o) of His's Nor-
mentafel and to Fig. XIX of those of Keibel and Elze; its nape-
breech length was 11.3 mm. and its age was estimated by RabI at
thirty to tliirty-one days. In the head the
fore-brain region is markedly prominent;
below the forehead the area triangularis
(His) projects, and below the middle of this
there runs what is only a moderately broad
groove through the mouth opening into the
palate, separating the medial nasal processes,
which at their first appearance were so far
apart. The two nasal openings are not only
relatively but absolutely nearer each other
than in the preceding stage, and look directly
forward. The lower ends of the medial nasal
processes, which are uniting with the maxil-
lary processes, are separated by a, slight de-
embno'o[g.3mm*NL!B4^ prcsslou from the lateral processes and are
™.'u%.rit^ndfe™n^oiiy ^^'^ proccssus globularcs (His). The lateral
'",''?'; 3^^y?*"" """""" nasal processes are consequently excluded

t.fdQfK«bel»ndElK,hB™ „ ^u e *■ e i\, i, j c

FiB.«,) from the formation of the upper boundary of

the mouth, which becomes the upper Up.

Pig. 65 shows the face of a 15 mm. embryo from in front,

after Retzius. The upper lip is still divided, the nasal septum

is still somewhat incomplete, and the processus glohulares are still

84 HUMAN EMBRYOLOGY.

visible. From the upper angle of the nose two folds run from above
and medially downward and laterally, the medial one passing to the
angle of the month; these are the oblique -maxillary folds, that is
to say, the nasolabial and the sub-
orbital folds. The ej^es are directed
distinctly laterally and are compar-
atively wide apart ; the mouth is
verj' wide ; and at the middle of the
lower jaw the anlage of the chin is
visible, although the lower jaw and
chin are as yet very poorly devel-
oped.

Figs. 66 and 67 show the head
of an embryo of 18 mm. en face and
in profile (after Eetzius). The view
en face appears rather remarkable;
Retzius thinks that the embrj'o may
not have been quite normal, but gives
no further reason for such a sup-
position. The description given of
the preceding emiirj'o will answer
for this one also, if it be added that
the nasal septum is now completely
FiQ. 64.— Head of ui ombryo which formcd. lu the pfofile view the posi-
C^™^tur£Xi'I^/Ei»!?™Fii' tion of the ear should be noticed; if
521. xio. (From c. Rabi. i. c). the mouth cleft be produccd dorsally

the ear would He below it.
Figs.' 68 and 69 show profile and en face views of the head of
a fetus of about eiglit weeks and 25 mm. in length (after Retzius).
The eyelids are in process of formation and
supra-orbital folds aJso occur, in addition to
the nasolabial and suborbital. The supranasal
groove is strongly marked. The distance be-
tween the eyes is still considerable, and they are
distinctly directed laterally.

Figs. 70 and 71 represent the head of a
fetus 42.5 mm. in its greatest length (ninth
week), in profile and en face. In the profile
view the great development of the forehead
region is striking, and below this the root of the ^'br^^^Tis^mm"'

nose is deeply depressed. The nose is still low, aeeaeniaa. xs. (After
but the lower jaw and chin are well marked. The xVi, F^i""!,) ' ' ' **
eyes are completely closed by the lids, but the
distance between the inner angles of the eyelids is very consider-
able; from medially and above the interpalpebral fissures are
directed laterally and downward. The upper eyelid is relatively

DEVELOPMENT OF HUJIAN EMBRYO. 85

small and is bounded above by a aharply-marked arched groove
and below by the interpalpebral fissure; from the inner angle
of the eye a supra-orbital groove extends obliquely laterally and

Fioa. ee ukI 67.— Hcwt of an embrya of I

PUM XVI. Flo. 3 and 1.)

X 2.5. (AfUr Ketni

Fioe, 70 and 71

i( 42.5 mm., seen en lace and
Plate XV[. PiiB. SaD<10.

X 2.5. (A(Ur Retiiiu, [. c„

Upward. The nose is ven,' broad in proportion to its height
(172:100), and the external nares are closed by the epidermal
plugs which are continuous with an epidermal thickening on the
upper lip.

86 HUMAN EMBRYOLOGY.

Finally, the profile view of the head of a fetus 117 mm. in
length may be shown {Fig. 72), and in it I would draw especial
attention to the projecting upper lip and the receding chin, to the
double lip, and to the shape of the nose. The pinna has almost the
position it holds in the adult. Witii regard to the mouth it may be
observed that the vertical median furrow which becomes the phil-
trum appears in the fourth month. The wall-like projecting
margin of the upper lip is separated from the inner portion,
which in the fourth and fifth months shows more or less projecting
tubercle-like elevations. The middle portion of the margin early
becomes the tuberculum labii superioris. In a similar manner the
wait-like margin of the lower lip becomes delimited from the inner
portion. In the first half of the third mouth the two lips project
about equally, but later the border
of the upper lip and the lip itself
grow more rapidly, so that in the
fourth and fifth months it projects
markedly beyond tlie lower lip; by a
stronger growth of the lower jaw and
lip this difference is gradually over-
come in the sixth to the ninth months,
but by a kind of inhibition process tlie
early fetal arrangement may be re-
tained in the adult to a marked de-
gree. Retzius has given especial at-
tention to the time of occurrence of
individuality, and comes to the con-
„ , ' , , , elusion that in man it is recognizable

Fro. 72. — H«d of m fetiu of 117 ■ 4.1, j> 4.1, il 5 ■ i_„

mm., in praflie. NMumi site. (A(wr eveu lu the fourth mouth of lutra-
Retiiiu. I. c. pi«w XVII, Fig. 10.) uterine life, and becomes more marked

in the succeeding months.

The first phases of the development of the extremities up to
the formation of the fingers and toes have already been considered
in connection with the development of the entire embryo; an
account of the further changes in the hand and foot may now be
presented, the descriptions given by Eetzius being followed
closely.

Tlie hands, after the fingers are formed, early assume their
human form and even in the third month have acquired their most
important characters; they are then comparatively broad and the
fingers are flexed. Of the persistent palmar furrows only the
largest, the lines of Venus and Mars, are distinct in the third
month. Four distal metacarpal pads (touch pads) appear at the
beginning of the third month opposite the interdigital clefts, and
in the course of this month they develop into strongly marked
elevations. In addition, there is a distinct ulnar marginal pad on

DEVELOPMENT OF HUMAN EMBRYO. 87

the metacarpus and one or sometimes two carpal pads. On the
terminal phalanges strongly prominent, hemispherical touch pads
develop. These, as well as the metacarpal
pads, become relatively lower in the fourth
and fifth months, and their boundaries be-
come gradually more indistinct; only in
individual eases do they persist in a- more
evident form with the later half of the
fetal period. The feet are always some-
what behind the hands in their develop-
ment. Even long before the separation of
the individual toes by the interdigital
clefts the abducted position of the great
toe is striking; and verj- earlj", even in
the second month, the prominence of the
heel is recognizable. The great toe is
from the beginning somewhat thicker and
the little toe somewhat smaller than the
other tliree. The soles, like the palms, are
at first directed medially, and consequent-
ly are opposed to one another. The dor- . J^^-JhrJ!!.' ^* t^'^.^l
sum of the foot is relatively very high in
the third month, and also broad towards
the roots of the toes. Compared with their position in the adult
the feet as a whole have now an " oblique " position (the varo-
equinus position); the arch of the sole is beginning to develop.

Fio. 74.— The poalerior end ot a fetus of 25 mm., »een from the dora»l surfaoe. X 10. (After Rflliit

88 HUMAN EMBRYOLOaY.

During this time, at tlie beginning of the third month, a row of
distal metatarsal pads appears as four or five roundish or oval
elevations, and one soon sees clearly that they lie opposite the in-
terdigital clefts ; it seems as though a shifting toward the lateral
(fibular) side occurred. In the next stage, that is to say,in the latter
half of the third month, there are four metatarsal pads which cor-
respond to tlie interdigital clefts, the fifth seems to have shifted
proximally on the lateral border of the foot. At this time the four
first-mentioned pads are relatively at their highest stage of devel-
opment, and simultaneously the pads on tlie terminal phalanges
have developed to liemispherical plantar elevations. In the fourth

Fiae. 75 and 76.— The right ai
fucea. XI

and fifth months the distal metatarsal pads undergo a relative
retrogre.ssion and their outlines become gradually indistinct; the
phalangeal pads remain well marked, although their outlines be-
come less pronounced.

Some figures may make these points clear. Figs. 73-76 repre-
sent the extremities of a fetus of 25 mm. Fig. 73 shows the right
hand from the volar surface with the touch pads ; Fig. 74, the two
lower extremities seen from behind and dorsally. The feet are
seen from their fibular borders, and their plantar surfaces are
turned toward one another. The high dorsum and the malleolar
eminences should be noted. Figs. 75 and 76 show the right foot
from the dorsal and plantar surfaces; the abducted position of the
great toe and the metatarsal touch pads cannot be overlooked.

DEVELOPMENT OP HUMAN EMBRYO. 89

Fig. 77 shows the sole of the right foot of a fetus of 44 mm.
with its touch pads; Fig. 78 represents the middle finger of a fetus
of 52 mm. from the side.

In the descriptions of the development of the face, hands, and
feet the conditions in the fetal
period have already been con-
sidered. For the development of
the form of the rest of the body
reference must be made to Gus-
tavRetzius (l. c).

Retzius has been the first to study
thoroughly the proportions of the human
body during the fetal period, and a reaumi
of his most important results may bring
this chapter to a close." He finds as fol-
lows :

i. The entire body length, measured
from vertex to heel, increases during the
fetal period to a greater extent than the
vertex-breeeh length, that is to say, the
lower limbs continually increase in length.

2. The relation of the height of the
head to the vertex-breeeh length, gradually
diminishes.

3. A comparison of the length of the
entire vertebral colmnn with the height of
the head and with the different regions of
the column shows that:

a. The height of the head diminLshea
relatively to the length of the vertebral 44 mm.'. .... ,

column. (After RetiiuB, (. c, Sale XXIV. Fij. 8.)

b. In general, only a slight change

can be obser\'ed in the ratio of the cen'ical vertebrtB to the entire column, al-
though there is a certain tendency towards a relative shortening of the cer\'ieal
vertebrte in the earlier stages.

c. Scarcely any change, apart from individual
^^_— ^^M^w*"— — variations, can be seen in the relation of the thoracic

^iJ\ . vertebne to the entire column.

t. {3b^^L. ''■ "^''^ relation of the lumbar vertebne to the en-

^liii^^^^^'" tire column shows no appreciable change.

F,a 78 _ The middle ^' "^^^ relation of the sacrococcygeal vertebrffl to

fingeroitiieright hand of a52 the entire Column also shows no material change; indj-

mm. fetu»,^9een^rrra '^^^^sl"^ vidual variations are, however, especially great, and the

i.c.'piateXXlV, Fig. Sa.i difficulties in the way of making exact measurements

are worthy of note.

4. The relation of the circumference of the head to the body length diminishes
from the earlier stages.

5. As regards the relation of arm length to body length, it was found
that during the seeond and third months the arm grows to snch an extent that
often even in the third month, and more certainly in the fourth and beginning of

" Compare also Chapter VIII.

right Tdo

90 HUMAN EMBRYOLOGY.

the fifth, it reaches its greatest relative length for the fetal period, its first
maximum (37-42 per cent, of the body length).

6. As regards the relation of the upper extremity to the lower and of the
leg length to the body length, it may be said that the lower limb grows more
slowly than the arm during the fetal period; at the end of that i>eriod it is
scarcely as long as the arm, but after birth it soon surpasses it. The relative
maximum of length for the fetal period (36-39 per cent, of the body length) is
acquired by the leg at about the fifth month.

7. A comparison of the arm length with the lengths of the upper arm, forearm,
and hand shows that:

a. During the period from the third to the tenth month the upper arm
is about 39-42 per cent, of the entire arm length.

h. In the relation of the arm length and that of the entire distal part of
the arm (foreami and hand) there are no perceptible changes either of progression
or regression during the fetal period.

c. Also the arm length compared with the forearm length (without the
hand), and

d. The arm length compared with the hand length show no noteworthy
changes of proportion dunng the fetal period.

8. The relations of the length of the lower limb to those of the three
portions of which it is composed may be stated as follows:

a. The relation of the thigh length to the leg length shows no noteworthy
changes from the third to the tenth month.

b. In the relation between the leg length and that of the crus (omitting the
height of the foot), a slight relative elongation of the crus is evident about or
before the middle of the fetal period.

c. In the relation of the length of the foot to the leg length there is a
definite relative elongation of the foot, especially from the sixth to the eighth
month.

9. In the relation of the breadth of the iliac crests to the body length no
actual change occurs during the fetal period from the third to the tenth month.

10. As regards the proportions of the head and face during the fetal period,
Retzius' results are as follows:

a. Ratio of head length to head width: In the first months, while the
cerebral hemispheres are still developing posteriorly, no measurements can be
obtained that allow satisfactory comparison. Notwithstanding that Retzius worked
with Swedish embr>^os and that the Swedes are a typically dolichocephalic race,
it seems that there is a strong tendency to brachycephalism and, indeed, to a
quite high degree of it.

b. Ratio of head length to head height : This index is very high in the
early months (112.5, 111.1, 100, etc.); it is still high in the third month (108.5,
104.2, etc.); but toward the end of this month it sinks (86.0, 81.6), and remains
at about the same level from the fourth to the seventh months, with only a few
individual variations upwards. If the figures given above are interpreted according
to the standard employed for adult skulls they all denote hypsicephalism (75.1
and over).

c. Ratio of head length to head circumference: In general, the circum-
ference of the head is about or almost three times as great as the length. The
index, which at first is smaller, increases during the third month to this value and
remains about the same, with indiridual variations, to the seventh month.

d. Ratio of head ^ridth to head height : This index shows a definite tendency
to diminish, apart from individual variations.

e. Ratio of head circumference to face height: The figures show no
regular change until the seventh month; it is remarkable that during these stages
iilmost the same values recur.

VII.

THE DEVELOPMENT OF THE EGG MEMBRANES
AND THE PLACENTA; MENSTRUATION.

By otto grosser, PEAauE.

I. INTRODUCTION.

The difficulties in the way of a comprehensive description of
human placentation have been mentioned so often that a detailed
re-enumeration of them is unnecessary here. The first stages, so
necessary for the understanding of all the later ones, are lacking,
just as they are in the case of the formation of the germinal
layers, and, as in this case, must be conjectured by deduction and
analogy. In the following description an endeavor will be made to
state what has been determined with certainty, and, in connection
with this, to call attention to disputed questions and to the probable
significances of the phenomena described.

A statement of our knowledge in the field of comparative
placentation may also be dispensed with, since it has repeatedly
been given in detail within recent years.^ The position which
man occupies among the Mammalia on the basis of the structure
of the placenta may, however, be indicated; and, in connection
with this, the nomenclature employed in placental classification
and the general morphological and histological processes involved
in the formation of the placenta may be described.

Placentation is (in mammals) the intimate union (apposition
or fusion) of the mucous membrane of the uterus with the outer
layer of the ovum, the chorion, which becomes vascularized from
the allantois ^ for the purpose of providing for the respiration and
nutrition of the embryo and for carrying away its waste products.

* 0. Schultze: Grundriss der Entwicklungsjjeschichte, 1897; Strahl: Embry-
onalhlillen der Sau^r iind Placenta, in Hertwi^s Handbuch, 1902; Bonnet: Lehr-
buch der Entwickliingfs^schicbte, 1907, and, most recently, 0. Grosser: Vergleich-
ende Anatomie und Entwicklungsgreschicbte der Eihaute und der Placenta,
Lehrbucb fiir Studierende und Aerzte, Wien, 1909. From this last work the
majority of the illustrations of this chapter have been taken. A very complete li^t
of the literature on human placentation is to be found in the work of F. Keibel
and C. Elze: Normentafel des Menschen, Jena, 1908.

'In some mammals also from the yolk sack. According to the view of
Hubrecht (see especially Resink, Tijdschrif t Ned. Dierk. Vereen, 1903, 1905 :
Hubrecht, Quart. Joum. Micr. Sc, 1909), however, the chorion possesses from the
beginning a vasifactive mesoderm. Compare Grosser's Lehrbuch.

91

92 HUMAN EMBRYOLOGY.

Since the union of the chorion and the uterine mucous membrane
is either an apposition or a fusion, the expulsion of the chorion
sack after birth either may take place without injury to the uterine
mucous membrane or a portion of the latter, the decidual mem-
brane (membrana decidual may be expelled with it; hence the
old division of the Mammalia into the lower Adeciduata and the
higher Deciduata. But tissue destruction frequently takes place
during pregnancy in the former, and, on the other hand, in many
highly organized forms the placenta contains no considerable
quantity of maternal tissue, if the maternal blood be disregarded,
so that in these it is hardly proper to speak of decidua (Strahl).
Accordingly, Strahl ^ has employed the relations of the maternal
blood as a basis of classification and has designated these
placentae *4n which post partum the spaces of the placenta which
carry maternal blood are separated and expelled" complete
placentce or placentce verce; while those simpler placentae, in which
during and after birth the maternal blood-spaces remain intact,
are termed half placentce or semiplacentce. The classification pro-
posed by Robinson (1904) is practically the same, since his ^* ap-
posed placentae" include those in which there is merely an apposi-
tion of the chorion to the uterine mucous membrane, while those
in which there is fusion of the two he terms ** conjoined placentae."
In the same way the two groups proposed by Assheton (1906),
that of the placentce plicatce with simple, non-proliferating
chorionic epithelium, and that of the placentce cumulated with a
greatly proliferated and thickened chorionic epithelium, traversed
by lacunae for the maternal blood, agree essentially with the
two divisions of Strahl.

The idea of placental types which the author ^ has conceived
takes its origin from another standpoint. The nutritive material
which passes from the maternal blood into that of the fetus in
the lowest types of placentae passes in succession through maternal
endothelium, connective tissue, uterine epithelium, portions of the
uterine cavity, the chorionic epithelium, chorionic connective tissue,
and the endothelium of the chorionic vessels. At the commence-
ment of development all the maternal walls are present in the
highest types of placentae also. But while the fetal layers are
always retained, or, in the highest types, are gradually formed,

* As a rule, however, the term decidua is not only applied to 'the superficial
layer which is expelled, but also includes the entire thickness of the mucous
membrane. This is the case with its application to the human placenta.

*In Hertwig's Handbuch, 1902, and recently in a fuller somewhat modified
statement in Der Uterus puerpuralis von Erinaceus europcetts, Verhandl. K. Ak.
Wetensch., Amst., 1907.

'Verb, morph. Gesellsch., Wien, 1908; Zentralblatt fiir Physiologie, 1908;
and Lefirbuch.

DEVELOPMENT OF EGG MEMBRANES AND PLACENTA. 93

during the early stages of development, the maternal partitions
disappear one after the other in the course of the phylogenesis
or ontogenesis, the chorionic epithelium penetrating farther and
farther toward the source of its nutrition, the maternal blood.
But the blood spaces themselves, those of the mother on the one
hand and those of the fetus on the other, remain sharply separated
under all circumstances. The penetration of the fetal tissue may
halt at any stage and so determine the structure of the mature
placenta and also the name which may be applied to it, this indi-
cating the maternal tissue which is in immediate contact with the
chorionic epithelium. At the beginning of the series stand
placentae such as those of the pig, in which all the maternal parti-
tions are retained; the uterine and chorionic epithelia are in con-
tact; and the placenta is a placenta epitheliochorialis. If the
maternal epithelium disappears, at least to a considerable extent,
as in the ruminants, the chorionic epithelium comes into contact
with the connective tissue and a placemta syndesmochorialis is
formed. If the connective tissue also disappears, so that the
chorionic epithelium is in contact with the endothelium of the
maternal blood-vessels, as is the case in the Camivora, according
to Schoenfeld, then the placenta is to be termed a placenta en-
dotheliochorialis. And, finally, if the endothelium disappears, so
that all the maternal partitions have vanished and the maternal
blood directly bathes the chorionic epithelium, then the highest
possible stage of placentation has been reached and the placenta
is a placenta hcernochorialis. Thus the most important morpho-
logical character of a placenta is directly indicated by its name.

The further subdivisions may, following Strahl, be based on
the form of the placenta. Thus there may be recognized a
placenta diffusa^ in which the chorionic proliferations or villi are
uniformly distributed ; a placenta multiplex, with the villi arranged
in groups; a placenta zonaria, in which they have a girdle-like
arrangement ; and a placenta discoidaUs, in which they are aggre-
gated to form a disk-like structure. The last group, which in-
cludes the highest types of placentae (the haemochorial of the
classification given above), may be divided, again following Strahl
(1905), into labyrinth placentce, with narrow capillary-like channels
for the maternal blood, and bowl placentce (placentce olliformes)^
in which the maternal blood has the form of a large sinus, the floor
of the space (bowl) being formed by decidua and the roof by the
chorion, from which the villi project, into the space.

The human placenta is a placenta vera (conjugata, cumulata)
discoidalis ollif ormis, or, according to my nomenclature, a placenta
hcemochorialis discoidalis olliformis. It represents the highest
development of its type, a development which even the placentae
of the anthropoid apes have not quite reached.

94 HUMAN EMBRYOLOGY.

The nutrition of the embryo takes place, in general, in two
ways : on the one hand, by the transference of nutritive material
from the blood of the mother to that of the child ; and, on the other,
by the direct absorption by the chorionic epithelium of products
of the maternal mucous membrane, these products frequently
being subjected to a kind of digestive process before they pass into
the embryonic circulation. These maternal substances are partly
products of secretion, partly waste products, together with extra-
vasated maternal blood, and have been included by Bonnet under
the term embryotrophe and by English authors have been desig-
nated pabulum. In the lower types of placentae the embryotrophe
plays an important role throughout the entire duration of preg-
nancy; in haemochorial placentae, and therefore in man, we find
(as has been noted, for instance, by Pfannenstiel and Jung), at
the beginning of development, up to the establishment of a definite
circulation in both the maternal and fetal blood spaces, a very
distinct absorption of embryotrophe consisting of degenerated
maternal tissues, while later, embryotrophe is entirely wanting, at
least in the region of the placenta.^ In haemochorial placentae,
therefore, two phases or stages may be distinguished : an embryo-
trophic phase, at the commencement of development; and a later
hcemotrophic phase, not sharply distinguished from the former in
time, but during which the nutritive material is received from the
maternal blood exclusively.

This absorption of material cannot, however, be regarded as
a simple process of diflfusion. This could be the case only with
crystalloid substances at the most; colloids, on the other hand
(such as the albumins, for instance), are taken from the maternal
blood by a process of resorption, associated with a partly con-
structive and partly destructive activity on the part of the
epithelium of the villi; and certain highly complex substances,
such as many immunity substances, cannot pass the placenta at all.
The chorionic villi of the placenta have a certain similarity to the
intestinal villi (Hofbauer), the maternal blood corresponding to
the digested food material. Up to the present the wandering of
fat, glycogen, and iron, the last as haemoglobin or its derivatives,
has been followed histologically from the maternal blood through
the chorionic epithelium into the fetal vascular system. The fat,
which penetrates into the chorionic epithelium in a state of solu-
tion (saponification), is reconverted into fat globules within the
epithelium at the bases of its cells.^ The haemoglobin comes from

*A modification of this statement is necessary in connection with the
maternal blood. See below.

' Holsti (1908) lays special weight upon fatty de^neration of the decidna,
upon fat formation in the glands, and npon the transportation of fat from other
orerans by leucocytes; this fat is directly absorbed by the chorionic epithelium
up to the close of pre^ancy.

DEVELOPMENT OP EGG MEMBRANES AND PLACENTA. 95

the maternal blood-corpuscles which degenerate in the placenta
itself, perhaps in contact with the chorionic epithelium. Oxygen
is set free from the oxyhsemoglobin of the mother, probably by
ferment action (for further consideration consult Hofbauer and
Kehrer). The maternal blood, therefore, often assumes in later
stages, even in placentae of the highest type, the role of the embryo-
trophe, although not in a manner easily recognizable histologically ;
and also for this reason the term haemotrophic phase is justifiable.

In placentation many cytological phenomena occur that are
not observable elsewhere. The most striking are those that lead
to the formation of multinucleated masses of protoplasm. Bonnet
(1903) has brought order into the exceedingly confused nomen-
clature of these structures; he designates (Lehrbuch, 1907) as
syncytia, ** deeply staining nucleated masses of protoplasm formed
by the fusion of originally separate cells ; plasmodia, on the other
hand, arise by repeated nuclear division unaccompanied by cor-
responding cell division. . . . Syncytia and plasmodia are always
living and active formations, endowed with especially energetic
metabolism, together with histolytic or phagocytic properties, and
also with the power of amoeboid movement. . . . They may subse-
quently split again into separate cell territories. . . . Quite dif-
ferent are the deeply staining nucleated masses produced by the
confusion of originally distinct cell boundaries and by aggregation,
but which show unmistakable signs of commencing degeneration,'^
Such masses are termed symplasmata.

Syncytia and plasmodia are chiefly formed by fetal tissues,
namely, by the chorionic ectoderm ; symplasmata, on the contrary,
arise from the maternal tissues. Yet, for a precise definition of
the structure, mention should be made of its origin ; so we speak
of a syncytium fetale epitheliale, of a symplasma maternimi con-
junctivum, etc. If the masses in question remain relatively small
they are known as multinuclear giant cells or simply as giant cells;
the above classification is applicable to these also. Mononuclear
giant cells, which, however, never reach a special development in
the human placenta, are merely greatly enlarged cells, usually
derived from the fetal epithelium.

While extensive histological modifications may affect almost
all the constituents of the maternal mucous membrane and find ex-
pression there in the formation of the decidua mentioned above,
these modifications affect only the chorionic epithelium among the
fetal tissues, the chorionic connective tissue and vessels showing
great uniformity of condition. The chorionic epithelium has been
termed the trophoblast by Hubrecht; this distinguishes the ecto-
derm of the chorion from that of the embryo and that of the
amnion. In the region of all placentae belonging to the higher types
it shows, at least in parts, active proliferation phenomena. Where

96 HUMAN EMBRYOLOGY.

it comes into relation with the maternal tissues it usuallv becomes
transformed at its surface into a syncytium (according to
Hubrecht's terminology, a plasmodium), and this portion has been
termed the plasmoditrophoblast (Vernhout, the plasmodihlast of
Van Beneden), now more properly the syyicytiotrophohlast ; while
those portions in which the cell boundaries are still retained form
the cytotrophohlast (the cytohlast of Van Beneden).

The trophoblast in Hubrecht's sense is a morphological con-
cept, based upon the views of that author as to the phylogenesis
of the Mammalia; it occurs in all of this group and covers the
entire ovum: it may also enter into entirely passive relations with
the maternal mucous membrane. The term is not used in
Hubrecht's sense when it is applied to the proliferating tropho-
blast, as frequently happens in the literature.** This proliferating
portion of the trophoblast, which is provided with histolytic
properties and especially makes possible the formation of
placentae of the higher types, is quite different from the portion
known as the inactive trophoblast, and has been termed by Minot
the trophoderm. Only in man (and the anthropoid apes) do the
two ideas coincide, since in these cases the entire trophoblast un-
dergoes lively proliferation and is, therefore, converted into
trophoderm.

Finally, as regards the position of the ovum in the uterus,
different types are recognizable (Bonnet, 1903). The union of the
ovum with the mucous membrane is known as the implantation or
nidation. If tlie ovum remains in the main cavity of the uterus,
the implantation is termed a central one. This is the most fre-
quent type {Adeciduata, Carnivores, the rabbit, the lower apes,
etc.). If, however, the ovum becomes implanted in a furrow or
diverticulum of the uterus and subsequently is shut off from the
uterine lumen by a fusion of the lips of the furrow or diverticulum,
then the implantation is of the excentric type (hedgehog, mouse).
Finally, if the ovum penetrates into the mucous membrane by
producing a destruction of the uterine epithelium and develops in
the mucous membrane after the closure of the point of entrance,
that is to say, outside the cavity of the uterus, as in the guinea-
pig and in the rodent Geomys, then the implantation is of the
interstitial type. In man the occurrence of this last type has now-
been almost certainly proved.

In the last two types of implantation the ovum is separated
from the uterine cavity by a layer of maternal tissue, the decidua
capsularis. It arises in the first case by a fusion of the margins

•Hubrecht, however, in his earlier works (Plaeentation of the Hedgehog,
1890) employed the expression to denote only the proliferating chorionic ectoderm.
Compare Hubrecht, Science, 1904, and foot-note 2.

DEVELOPMENT OF EGG MEMBRANES AND PLACENTA. 97

of the walls of the furrow or of the lips of the diverticulum; in
the second case, by the fusion of the lips of the implantation cavity ;
and, in later stages, when the ovum bulges out toward the lumen of
the uterus, it covers like a shell the part of the ovum turned away
from the placenta.

II. MENSTRUATION.

Menstruation, which occurs at regular periodic intervals in
man and the apes, is the expression of changes in the uterine
mucous membrane which are associated with preparations for the
reception of a fertilized ovum. A consideration of it is therefore
necessary as an introduction to an account of placentation.

The mucous membrane of the corpus uteri has, in general, a
very simple structure. A single-layered, cylindrical or cubical
surface-epithelium, with varying amounts of ciliation (Mandl,
1908), simple or sparingly branched tubular glands varying con-
siderably in number in different individuals (Hitschmann and
Adler), a stroma with fine connective- tissue fibrils which are diffi^
cult to demonstrate by ordinary histological methods (Bjorkenheim,
Hitschmann, and Adler), and, finally, the entire absence of a sub-
mucosa — these are its most important characteristics. The ends
of the glands frequently penetrate to between the irregularly de-
fined innermost layers of the muscularis and so obtain for the
mucous membrane a firm adhesion to the muscularis and a well-
protected position for their basal portions, a circumstance of
considerable importance both intra and post partum.

Hitschmann and Adter • have shown by their comprehensive,
recently published observations, upon which are based the state-
ments that follow, that this mucous membrane is never in a com-
pletely resting condition in a fertile female. Growth and degener-
ation alternate regularly and form together a menstrual cycle of
normally twenty-eight days. The cycle may be divided into
certain more or less clearly marked periods or phases. The longest
of these is the interval (between two menstruations) or the inter-
menstrual period, which lasts for about fourteen days, during
which the mucous membrane is almost at rest and only undergoes
a very gradual increase in thickness. Upon this follows, without
a sharp limitation, the premenstrual period, which lasts about six
or seven days and is characterized by intensive proliferation and
swelling of the mucous membrane, finally leading to hemorrhages.
These last for about three to five days, the period of menstruation,
during which the mucous membrane again decreases in thickness
and undergoes extensive degeneration. In the remaining period
of the cycle, the postmenstrual period, of about four or six days
duration, the mucous membrane is regenerated.

•These authors cite the literature of the question.
Vol. I.— 7

98 HU5IAN EMBRYOLOGY.

The mucons membrane during the interval is in the condition
usually described as normal (Fig. 80). The mucosa is, on the
average, about 2 mm. tiiick ; in the fresh condition it is grayish red

Fio. 81. Fro.S2.

FiOB. 79-82.— Fiein*s "f the uterine mueoun membrftne in the various pluue*. Fig. 79. Poet-
meaBtruiil mucous membrBne. one dsy after menstruation. Fig. 80. Tlie condition during the interval.
Fig. SI. Prementtnial condition. Fis. 82. Condition on the third day of meastruation, shoving sepaia-
tioD of the superlicial layer. (After HitschDiann and Adier.)

and rather smooth. The glands have a slightly spiral course and,
for the most part, are directed obliquely to the surface, their lower
ends being, as a rule, bent upon themselves. Their lumina are
oirfiular in transverse section and at first empty. The gland cells

DEVELOPMENT OP EGG MEMBRANES AND PLACENTA. 99

are at first small with elosely-set nuclei ; but in the second
half of the period they become enlarged, their plasma becoming
homogeneous aod acidophilous. The stroma cells (Fig. 89) are
fusiform or stellate, with large nuclei, richly provided with chro-
matin, and possess but little plasma, so that the tissue resembles
adenoid or embryonic connective tissue. Lymphocytes and small
lymph-nodes occur in it.

^-fc^SHCC*"''***^

FiClB

83-87

-The torn

o

the

glude In the d

Ben

t piiagjB

ot menslruxion u

ider the MDie

nuwnificti

m. Fig. 83. A postm,

-usi glud. tmtii

and

longaud.

Fi«. 84. A glMid

val period.

pi«lly

Bed

Fig. 86. A premeDsi

in Koraticm

Fig

sa. Giund

the

third d»y of th.

toalper

od. one Mill of th

type, the ot

rseted u>

dr

m.ing. Fi«.87.

Olandfromkyo

ungdeoidua, wide,

Kith seoODdtry

■IveoUand

DitBnl

ion. (Afte

rH

tsch

p3Bnn and Adler

Already toward the close of the interval the gland cells begin
to produce secretion granules (Fig. 84), which are also expelled
into the lumina of the glands; and the stroma begins to show a
diminution in compactness and some oedematous infiltration.

In the premenstrual stage (Fig. 81) the mucous membrane
rapidly thickens to two or three times its previous thickness. This
depends partly upon an increase of the oedema, and partly upon

100 HUMAN EMBRYOLOGY.

an enlargement of the individual elements. This shows itself in
the gland cells (Fig. 85) by a swelling of the nuclei and of the
plasma and by abundant secretion, which produces a frayed ap-
pearance on the inner surfaces of the cells; the secretion, which
is also to be found in the lumen of the uterus, is now clearly recog-
nizable histologically as a mucous secretion and contains flakes of
the older, still acidopbilous secretion. The enlargement of the
cells produces, on the one hand, a formation of folds and ont-
pouchings of the walls of the glands, the stroma projecting like

FiQB. R8-ei.— The cyclic chansei of ths Btroma ceLli of the utBiine muooH. Fig. SB. PoAmen-
Btnul coni^tion. Fig. SO. Tbe CODdition occumng in the interval. Fig. 90. Premengtnjiil auiditioa
<BvB t« nx daya before the menBtruatioii). Fig. 91, Condition immediklely before meantnistioa.
(Afler HiliKhmanii ud Adier.)

papillae into the folds of the mucous membrane; on the other
hand, in conjunction with the secretion, a great enlargement of the
liunina of the glands results. In consequence, tbe walls of neigh-
boring glands are brought nearer together, the stroma being
compressed between them; and an appearance as if there was an
increase in the number of the glands is produced. The glandular
changes are most striking in the deepest layer of the mucous
membrane; in the superficial layer the stroma cells enlarge (Fig,
90) and become roundish or polygonal with a clear, feebly staining
plasma and large, also feebly staining nuclei; they represent a
preliminary stage of decidual cells (Fig, 91). By the localization
of tbe glandular changes, on the one hand, and those of the stroma

DEVELOPMENT OF EGG MEMBRANES AND PLACENTA. 101

cells, on the other, the mucosa is differentiated into two layers,
which, as in the case of the mucous membrane of the gravid
uterus, are designated, the deep one as the spongy and the super-
ficial one as the compact layer (compare also Fig. 92). The

latrua

.lion. SL hUDorrhs^int

lulanii I'd.. Elatul of the

(Kr.

former acquires a spongy consistency as the result of the great
enlargement of the glands, and the latter is characterized by the
closely packed, decidua-Iilce stroma ceils and the straighter course
of the glands.

Toward the end of the premenstrual phase there occurs an
engorgement and dilatation of the blood-vessels; and the mucous
membrane, which at first was pale, becomes bright red in color.

102 HUMAN EMBRYOLOGY.

Small hemorrhages occur at the same time ; these become confluent
and destroy the continuity of the tissue, subepithelial haematomata
are formed, portions of the epithelium are torn away, blood makes
its way to the surface of the mucous membrane, and the actual
menstruation begins.

With the onset of this there is an effusion of blood and of the
oedema fluid, on the one hand, and an expulsion of the glandular
secretion, on the other, whereby a rapid shrinkage of the mucous
membrane occurs. Frequently, but not always, there is also a
desquamation of the glandular epithelium. The outpouchings of
the glands rapidly disappear and these assume an almost straight
form with narrow or collapsed lumina (Figs. 82, 86, and 92) ; the
emptied cells become low and small. Of the stroma cells those that
have been most profoundly altered break down and are expelled
or carried away by leucocytes; the rest again diminish in size.
The surface epithelium may be for the most part retained, or,
even in normal menstruation, may be expelled together with the
greater part of the compact layer (Fig. 82), painful contractions
of the musculature aiding in the separation of this rigid swollen
layer; yet the epithelium is in all cases regenerated before the
close of the menstruation.

In the postmenstrual stage the mucous membrane is thin, with
almost straight glands (Fig. 83) and long, narrow, fusiform,
closely packed stroma cells (Fig. 88) ; little remains of the hemor-
rhages, and even these remnants quickly disappear. After a few
days the glands again become larger and begin to assume a wavy
outline, the stroma cells become more succulent, and the mucous
membrane returns to the relatively quiescent stage of the interval ;
nevertheless, in the first half of the interval numerous mitoses are
to be found in the glandular epithelium.

The similarity of the premenstrual mucous membrane to that
of the decidua indicates that the premenstrual changes (the loosen-
ing up of the tissue, enlargement, increased glandular activity,
swelling of the stroma cells, formation of two layers in the mucosa)
are a ripening process, a preparation for the reception of a
fertilized ovum, and that they are physiolo^cally the most im-
portant part of the entire cycle, while menstruation itself is only
a secondary process, a degeneration of the mucous membrane,
which from a failure of pregnancy has not been able to fulfil its
purpose.

As to the relation of menstruation to " heat " of animals, as well as con-
cerning the question of the occurrence of re^lar cyclical changres in the genital
mucous membranes, see, for example, W. Heape : " The Sexual Season of Mammals
and the Relation of the ' Prooestrum ' to Menstruation," Quart. Joum. Micr.
Science, vol. xliv, 1906 ; M. Van Herwerden : " Bydra^ tot de Kennis van den
menstrueelen Cyclus, Tijdschr. Nederlandsche Dierkundi^ Yereeniging, Deel, x,
1906: and the auto-abstract of the author: "Beitrasr zur Kenntnis des men-
struellen Zyklus," Monatsschrift fUr Geburtshilfe und G>Tiakologie, vol. xxiv, 1906.

DEVELOPMENT QF EGG MEMBRANES AND PLACENTA. 103

Bryce and Teacher (1908) lay special weight upon the possibility of an
implantation in any portion of the intermenstrual cycle (compare Sect. Ill),
and so reach the conclusion that the " menstrual decidua '' is not a preparation for
the reception of an ovum and that menstruation cannot be regarded as " the
abortion of an unfertilized ovum." The object of menstruation is merely to
maintain the endometrium at all times ready for the formation of a decidua; the
premenstrual tumidity and decidua are by chance similar, but actually are
merely degenerative phenomena of an over-ripe mucous membrane. Both periods,
the menstrual and the premenstrual taken together, are compared by these authors,
in agreement with Heape, to the phase of animal " heat " that the latter author
has termed the " prooestrum." During this the vulva is swollen and red, blood
and mucus exude from the vagina, but the animal is not capable of conception.
The time for conception, the " oestrus," corresponds to the postmenstrual period,
with its somewhat increased libido, observable also in the human species; while
the interval is equivalent to the resting stage in animals, the " metoestrum." This
view of the matter is difficult to reconcile with the histological phenomena of
menstruation; see also later. Section III.

III. OBSERVATIONS ON YOUNG OVA.

{Implantation^ the Embryotrophic Phase of Placentation^ and Transition Stages.)

Ova which, indeed, do not directly reveal the processes of
implantation, but are young enough to permit definite cod elusions
concerning it, are that of Bryce and Teacher (1908) and then that
of Peters (1899) and that of Leopold (1906). These preparations
show, on the one hand, the so-called implantation opening,^^ and,
on the other, the extensive proliferation of the chorionic ectoderm
or trophoblast which precedes the development of true chorionic
villi containing mesoderm. They do not suflSce, however, for a
certain solution of all the questions which suggest themselves.^ ^
Thus confirmation, based upon the study of older ova, is much
needed of the views regarding the mode of development of the
extensive intervillous space and of the formation of a double-
layered epithelium on the villi. Of modern, well-described prepara-
tions the thoroughly studied and very beautiful ovum of Jung

10

The implantation opening is also evident in some older ova (Graf Spee,
Beneke) ; in others, some of which are very young (such as that of Jung), it
is no longer so.

" The ovum of Leopold is undoubtedly extensively altered, so that while it
is of value for the confirmation of ideas derived from other ova, it is in itself
of little significance; the Peters ovum, whose discovery has effected a revolution
in our ideas of placentation, and the more recent ovum of Bryce and Teacher are
the most important sources of our infonnation concerning the beginning of
human development. That the ova described by older writers (Breuss, Allen
Thomson, and especially the celebrated ovum of Reichert) were younger, as Stratz,
for example, supposes, is very improbable, since the measurements of their egg
capsules were much greater. The methods by which these ova were studied were
too imperfect to allow wide-reaching conclusions; and the ova themselves need
not be further considered here. Furthermore, as regards the Reichert ovum,
Kolliker and later Hofmeier (1896) have, on sufficient grounds, reached the con-
clusion that it was not normal. (See also note, p. 104.)

1(M HUMAN EMBRYOLOGY.

(1908) is the most important; then the equally well-preserved
ovum of Siegenbeek van Heukelom, the first that was described
under the influence of the newer ideas concerning implantation
and placentation ; and the preparation of Frassi (1907 and 1908),
the study of which has led to conclusive information concerning
many of the processes succeeding implantation. Other important
objects are the young ova which Graf Spee (1905) and Beneke
(1902) exhibited at Congresses, but concerning which only quite
brief notices exist ; and, further, the thoroughly described prepara-
tions of Friolet (1904), Rossi Doria (1905), and Cova (1907), as
well as those of Pfannenstiel (1903) and Marchand (1903). A
very young, but unfortunately poorly preserved, ovum is that of
Stolper (1906). For a number of questions the older preparations
of Merttens (1894), Graf Spee (1896), and Leopold (1897) are of
interest.^ ^

The preparations considered here are arranged according to
their size in the appended table. Certain diflSculties, however,
become apparent in the arrangement, since the measurements
employed by the authors are not identical. ^^

AiifK/^- I Dimensions

^^^^<'^' iu mm.

Remarks.

Bryce-Teacher 0.63 ( XO.77)

Petera 1.6X0.9X0.8

Leopold
Stolper.
Graf Spee

1.4X0.9X0.8
2.5X2.2X1.0
2.5X1.5

Exclusive of epithelium (trophoblast).
Internal space of the ejrg capsule (exclusive of

trophoblast) .
Diameter of cavitj'.
Diameter of egg capsule.

Jung I 2.5 X 2.2 ( X 1.1) I Exclusive of epithelium (trophoblast) .

Beneke ' 4.2 X 2.2 X 1.2 Measurement of cavity of ovum.

Siegenbeek I 5.5X4.5 Including epithelium between the bases of the

I villi, but excluding the villi themselves.

Rossi Doria 6 X5

Frassi ' 9.4 X 3.2 Diameter of the cavit v.

Friolet 11-12x9

Cova I Em>)ryo with open auditory vesicles, anlagen of

! liver, hypophysis, etc.

" The number of young ova described in the literature is much greater. Of
well-preserved ova there may be mentioned especially those of Etemod and Hitsch-
maim and Lindenthal (figures of the latter in Schauta: Lehrbuch der gesamten
Gynakologie; and in the Lehrbuch by the author, already mentioned); but of
these thorough descriptions have not yet been published. The numerous ova de-
scribed before the publication of the works of Siegenbeek and Peters, few of
which were observed in situ, the majority being aborted or separated from the
egg capsule, are for the most part of little interest in connection with the questions
under discussion here, since up to that time the problems were imperfectly under-
stood. A mention of these ova would occupy too much space; compare the
comprehensive reviews of Peters, Pfannenstiel, and Frassi.

" The determination of any measurements from the figures is hardly ever
possible; the authors almost never state the magnification. A statement of the
objective and ocular, which is generally preferred, is worthless, since for deter-
mination of the enlargement the tube length, the height of the stage, and the kind
and dimensions of the drawing apparatus are also necessar>\

DEVELOPMENT OP EGG MEMBRANES AND PLACENTA. 105

Finally, some preparations of the attachment of the ovum
in atypical situations, such as tubal and ovarian pregnancies, are
of importance, since they offer opportunities for observing, as in
an experiment, tlie development under modified external conditions
and for separating fetal and maternal derivatives. To this group
belong, for example, the tubal ova of Fiith (1898), Pfannenstiel
(1903), etc., and the ovarian ova of Freund and Thome (1906),
Busalla (1907), and Bryce, Kerr, and Teacher (1908; tliis also
contains literature references),

A. REVIEW OF THE DESCRIPTIONS OF VOiNG OVA

OBSERVED IN SITU.

Tlie youngest known human oviim, that of Bryce and Teacher, was already

imbedded in the mucous membrane. It consisted of a loose, almost spherioal mass

of mesodenn, avera^iiiK 1-63 mm. in diameter, with wide intercellular spaces, but no

rccloui; in this mass were two small epithelial cavities (probably the medullo-

Fig. 93.— Transvi

rw Motion of the Bryce-Teacher nv»m (Verb. Aunt. Ges., 1908)

»how« "the point otealninoe, with a eonital man of fibrinous di

it, pmnting U> blutocya

; the implajilation csvily it bounded by a necrolic dcciduA laye

with UUUmtl blood. «b

amniotic and yolk-sack cavities) and it was enclosed by a tliick investment of
tissue, wliicii is probably to be regarded as chorionic ectoderm only, the trophoblast
shell (Fiff. 93). This shell, the blastocyst wall, consists (see Verk. Anat. Geseltsck.,
1908) (1) of an inner lamella in which the cell outlines are not sharply detiued,
the nuclei are *ery irregular in size, and many cells show double, treble or even
multiple nuclei; (2) of an extremely inegnlar formation which has definitely
plasmodtal characters. These two layers differ very markedly in the characters
of the nuclei and in tlie staining' reactions of the protoplasm, but they clearly
form parts of one formation. The cellular layer we name, after Hubrecht. Ilie
cytotn)phoblast, and the plasmodial layer, the pi a smodi trophoblast. The cytotropho-
blast is confined to the immediate wall of the blastocj'st, and tiiere is no sign of

106 HUMAN EMBRYOLOGY.

protrusions of tlie cellular layer into the strands of the plasmodiuni, although
at one or two points a minute bud of eytotrophoblast is seen estending outwards.

" The Plasmodium " foniis an extremely irregular network, the spaces of
which are Dlled with maternal blood (Fig. 94). Isolated masses of the formation
show a]l stagpes of vaeuolation, from niulliple small vacuoles to a spun-out reticular
condition. This vacuolation of the plasm odium is probably produced by the

Fia. 04. — BIsatoFyst wnll Kith cytotiophoblaiit and eyncytiiim, decidun, sod opening o( m dilated
nnu»-1ike rapilLary in the implantation CHVjty. cyl., eylatrophoblsxt: dtc., decidua; end., endoIhe)>iim of
s iDaternal capillBry; n. I., necrolic tone of the decidual p'-. [da>niadlum (siiicytium). X 2S0. (From
Bryce-ToMher, Plat* V.)

secretion of a fluid containing digestive ferments, which cause coagulation necrosis
followed by solution of the decidua, thus leading to enlargement of the im-
plantation cavity. As the vacuoles enlarj-e tlie plaj^modium is reduced to fine
strands, and when these break throtigh, the maternal blood lakes the place of the
secretion in the spaces of the mesh-work."

The oval cavity of the decidua, in which the o\'um lay, had diameters of

" Corresponds to the syncytium of Bonnet (p. 95), since it contains no nuclear

DEVELOPMENT OP EGG MEMBRANES AND PLACENTA. 107

1.9 X 0-95 X 1-1 mm, A small opening, closed by fibrin, and about 0.1 mm. in
diameter, placed the ca.vity in communication with the lumen of the uterus; the
opening was not covered by a blood-clot. The wall of the implantation carity, ex-
cept at points where maternal vessels opened into the cavity, was formed of necrotic
decidua and fibrin deposits. Only at individual points did the Plasmodium quite
reach the wall. The glands were enlarged and filled with blood, their epithelium
haWng separated; and the greatly dilated vessels form, especially beneath the
ovum, a regular cushion. The decidua is traversed by numerous leucocytes, and
all tlie portions of the uterine mucous membrane that were esamiaed showed

DlaoUtiooWiiy filled with blood. ,■; 3M. (F^[Il Bryoe-Teacher, FIbib VI.)

decidual changes. In the necrotic decidua zone around the ovum and also lying
free in the blood -containing implantation cavity was an almost continuous
peripheral layer of large, mostly mono-nucleated cells (Fig. 95), which are
perhaps to be regarded as degenerating decidua cells set free by the breaking up
of the necrotic zone."

"The comparison of these cells with a layer of fetal cells which occurs
upon the surface of the placental anlage in the guinea-pig, a comparison drawn
by the authors on the bafli.s <)f a demonstration by Graf Spec, does not seem to
be justified, since the cell layer in question (Duval's ectoplacental entodenu; see
also the author's Lehrbuch) owes its existence to tlie greatly modified inversion
of the germinal layers in the guinea-pig.

108 HUMAN EMBRYOLOGY.

The preparation was obtained from an abortion which occurred sixteen and
a half days after the only eohabitation that needs consideration and ten days
after the failure of the expected menstruation. Tlie microscopic picture is very
Strang* and striking and cannot be compared with any stages of placenta formation
known in animals;" it ii liowever, as the niithors state, qnite reconcilable with
the newer theoretical deduclions concerning implantation and the commencement

Fio. 86.— A wclion thnnuch Ihe Peters ovum and ihe ramninding ponionsof the uleriue inuwiu
membrsnc. Bl.. blood iBeunir: Ca„ capMuJariK; m.CAi., mesoderDiBlBxia of ihe first chorionic vifli; Co..
dfadua comparia; Dr., tilande; £., «mbryo; G.. malernal veiuels; Sc„ clof-rng onisuJuni IPeten<'s fungoid

capoulamexWDdafromalob. -50. lAfier Pelen^ ISOU. CompKrE' slw Fig. »7.>

of the placenta formation. Among the most sinking peculiarities in cumparisoa
with what is found in older preparations are ; ( 1 ) the structure of tlie trophoblast
shell; (2) the sniallness nf the implantation oj>eninp; (3) the necrotic character
of the wall of the egf; eliaraber and the absence of a mutual penetration of the
fetal and maternal elements. Whether the preparation can be regarded as

"Whether the extensive syncytial formation described by Strahl (1906) in
young stages of Miirmecaphaiia, Dasypus, Dendmhiirax. and Aluala, and by Duck-
worth (1!)07) in Maeacus, is comparable with that in the hnman ovum cannot be
determined, since Strahl gives no figures and (hose of Duckworth concern a
somewhat later Nlnge.

DEVELOPMENT OF EGG MEMBRANES AND PLACENTA. 109

absolutely Donnnl must provigionally be left undecided; it comes, on tbe one
hand, from an abortion, and, on tbe other, it was preserved only after having re-
mained for twenty hours in a mixture of urine and blood serum. Nevertheless,
mitoses are still distinguishable la the cytotrop ho blast cells, and the geaersl im-
pression furnished by tbe preparation, which was demonstrated at the Congress
of Anatomists at Berlin, 1908, is distinctly favorable. In the absence of other
equally young ova our views concerning placentation must, for the time being, be
brought into harmony with this preparation.

The conditions in the Peters ovum are quite different. The cavity of the
ovum contains the magma reticulare with the antage of the embryo and the
body cavities" (Figs. 96 and 07), and has diameters of 1.6X0-9X0.8 mm.; ex-
ternal to the chorionic mesoderm is a layer of closely packed cells, which is

Pio. 07. — Cytotropboblut and lyncytiuDi of the Peon ovum. The embryonie >truiituT«9 an shown
dii«nunm«ticallv. Ah,, uvmaiie avity: Dt., yolk mck; Ic.-H.. inUrcellulmr c&vitiaa ol the meiodemi;
U.. body cavitiei (cf. Groaser: Lehrbuch); M. r„ tn««au reticulare; Sy.. lyueytium: Tr., (cytoltropho-
bilM. (From Peten. Plate I, copied under control of the preparatioD ilMlf.)

traversed by wide blood spaces and surrounds the entire ovum like a shell or
mantle having a thickness of 0.5 mm. or more. Into this cell mantle, which is
thicker toward the muscularia than toward the surface of the mucous membrane,
there project everywhere short, stout processes of the mesoderm, the anlagen of
the mesodermal axes of the villi. The cell mantle, on account of its relation to
the mesoderm of the ovum, can hardly be interpreted otherwise than as the
chorionic ectoderm, trophoblast, and trophoderm."

Peripheral to this trophoblast shell lies a layer of tissue which Peters terms
the transition zone and which contains, imbedded in an (edematous stroma, a
confused mass of maternal, and apparently also of fetal, cells, together with a
large number of free blood-corpuscles. The entire ovum, without projecting
beyond the level of the mucous membrane, lies beside a fold of the membrane.

" For details concerning the formation of tbe body cavities of the Peters
embryo consult Grosser's Lehrbuch.

"Compare, however, the ovum of Beneke described below, and Disso's in-
terpretation of it.

110 HUMAN EMBRYOLOGY.

imbediJed in the decidua compacta, which over tbe dorsal surface, the summit of
the ovum, is defective over an area of about 1 mm,; throughout this region the
uterine epithelium, elsewhere well preserved, is wanting. The egg does not project
through this defective area freely into the uterine lumen, but is separated from
it by a fibrin clot that closes the opening in the compacta and spreads out lateralis
like a fungus growth (Figs. 96 and 98). This clot b termed by Peters the fungoid
tissue or blood-fungus, and later by Bonnet tbe dosing coagulum.

The decidua over tbe entire surface of the uterus is high and swollen, and
is divided by furrows into distinct areas; its separation into compact and spongy
layers is distinct only in the neighborhood of tbe ovum, for, although enlarged
glands with epithelial papillffi occur elsewhere, yet these occupy almost the entire
thickness of the mucous membrane, so that a superficial compact layer is not
distinct. Typical decidua cells cannot be found, although some large cells of

FiQ. 08.— Summit o( lli« PoWn ovum. BL, blood Ucun«; Co., capnuluie: &., oli _ _ _ .
St., iUiUlk; Sv., syncytium; rr., trophoblut; (7*.. uterine epithelium: l/c.R., the crumpled bolder of
this; a., cropboblKt aucleue in the syncytium; b. sod c, preparatory stagea of the syncytium (wreath-like
depont in ■ blood taauna-J (From Peters, ISBB.J

irregular shape and with large, deeply staining nuclei occur in the vicinity of
the ovum; the significance of these is, however, obscure. The entire mucous
membrane, in which very greatly enlarged blood-vessels occur, especially in the
neighborhood of the ovum, shows signs of edematous infiltration, which increases
in distinctness nearer the ovum; in this region extravasated red and white blood-
corpuscles also occur. A new formation of blood-vessels occurs especially in the
zone of tissue which intervenes between the ovum and the uterine lumen. The
glands in the neighborhood of the ovum cun'e around this and open near it
upon the surface of the utena; beneath the ovum are closed glandular spaces
filled with blood, which show no connection with the e^ capsule.

A number of important points are slill to be noticed concerning the tropho-
blast layer. The principal part of tbe layer consists of completely separated cells
with pale protoplasm and large, deeply staining, round or oval nuclei. On account
of the size And staining properties of the nuclei the entire trophoblast shell appears
dark even under weak magnification. Throiighout its entire extent it is traversed
by blood lacunffl, some lai^ and some small, which are continuous one with the

DEVELOPMENT OP EGG MEMBRANES AND PLACENTA. Ill

other; these lacune, some of which approach so closely to the chorionic mesoderm
as to be separated from it only by one or two layers of cells, are everywhere com-
pletely filled with well-presen-ed matertiat blood. At various places they are in
cotmection with venous vessels, which possess an endotlielial wall only in the
transition zone; the opening of arteries or capillaries into the lacunee cannot be
made out. " The most peripheral lacun» are, for the most part, separated from
the decidual tissue by a thin covering of ectoblast arranged in concentric layers;
but in places diverging tracts of trophoblast stream out into the compacta, and
the blood spaces lying between these lack the ectodermal covering on their periph-
eral surfaces," In the most central portions of the trophoblast cells are to be
found wilh feebly staining and distended nuclei, with vacuoles, nuclear fragments.

Fio. «9.— A portion of the peripherj- of the trophublMt sh»ll of the Peten ovum. Degenerating
patsheB of syncytium with greatly enlnrged nuclei; tbe blood-corpusclea, for the mont part, only mtiag
npon tbe lyooytium. Tr., cytotropboblaat; Ui., encloaiug lone. x 360.

and flakes. More peripherally the distention and degeneration of the nuclei in-
creases, the cell boundaries vanish, and there are formed very irregular, large,
vacuolated masses of protoplasm, with numerous, irregularly contoured, and ex-
ceedingly large nuclei (Figs. 99 and 102). These masses constitute the syncytium
of the Peters ovum, which is, accordingly, united by all possible transitions with
the cellular trophoblast; it is never separated from this by a limiting membrane.
Prickle processes cannot be seen; at most there is " a delicate and thin, strongly
refractive deposit, slightly frayed at the edges, on the surface of thfe syncytium."
The syncytium completely clothes, except at a few ]>laces, the blood lacunie with
a thin layer; indeed, according to Peters, the formation of the syncytium seems
to be produced by the contact of the trophoblast with the maternal blood. Further-
more, it would seeni, according to his ideas, that degenerating red and white blood-
corpuscles may be " transformed " into a syncytium, which applies itself to that
formed by the trophoblast, so that the blood with its own stnictural elements may
be concerned in the formation of the syncytium (compare Fig. 98, " wrealh-like

112 HUMAN EMBRYOLOGY.

deposits in the lacune representing preliminary stages of the syncytium ")." Tlw
syncytium occurs, as a rule, only at regions where there is contact with the maternal
blood. Trophoblast and syncytium are frequently mingled with elements of the
maternal tissues in the transition zone, and, like these, undei^ degeneration in
that region, since free maternal and fetal nuclei can be found in it; the tropho-
blast and syncytium also frequently replace the wall of a gland and project into
its lumen, and they may form the walls of the maternal blood-'Vessels in the
peiipheral portions of the trophoblast shell — sometimes by forming one wall of
the vessel while Ihe opposite one remains formed fay normal epithelium, sometimes
in that over the entire wall only the epithelium, either intact or in fragments,
separates the syncytium from the cavity of the vessel (Fig. 100). A transition
between the endothelium and the syncytium is never recognizable.

Peters's preparation was obtained from the uterus of a suicide, poisoned by
caustic potasli on the third day after the omission of a menstrual pmod. The

through At two places (a And
endothelium; En., eudotheli
ium," (After Peters, 1890.)

mode of death may not have been without influence on the blood engorgement
of the uterine mucous membrane. Peters estimates the duration of the pr^nanc;
at from three to four days; details concerning this are given elsewhere. The
preservation of the ovum (the autopsy was performed a few hours after death)
with the exception of the caudal end of the embryonic aniage, was very good,
even although mitoses are not recognizable in the trophoblast cells.

The Leopold ovum, which was obtained from a case of phosphorus poisouing,
concerning which further data are not available, differs in several points from
that of Peters; Thus, the trophoblast growth was less extensive ; and the blood la-
cunte, which were in open conneetioii with the neighboring capillaries, were unusually
wide. The trophoblast cords were, for the most part, reduced to one or two layers
of cells, and were to a lai^ extent covered by syncytium. In addition to the
ovum, separated portions of the syncytium were also to be found in the decidua,

" Peters, in a private communication, now regards these and similar structuree
as rather the expression of embiyotrophic processes.

DEVELOPMENT OF EGG MEMBRANES AND PLACENTA. 113

having evidently wandered into it; but, on the whole, there was less syncytium
than in the Peters ovum, and its individual parts were smaller. It was every-
where clearly distinguishable from the vascular endothelium. The contents of the
trophoblast shell, the mesoderm of the ovum, were irregularly shrunken and con-
tained maternal blood-corpuscles; an embryonic anlage could not be distinguished
(it had probably been already destroyed). The internal diameters of the cavity
of the ovum were 1.4 X ^-^ X 0.8 mm. This ovum was also imbedded, somewhat
superficially, in the mucous membrane in the neighborhood of a furrow, but a
differentiation of the mucous membrane into compacta and spongiosa was not
distinct. The regions surrounding the ovum were very rich in glands, which
curved around the ovum. Dorsal to the ovum the decidua, in contrast to that of
the Peters ovum, is closed except for a small opening, so that a decidua capsularis
is present. Extending outward from the opening upon the surface of the mucous
membrane is a clot, consisting of blood and fibrin, which corresponds to the fungoid
tissue or closing coagulum and is termed by Leopold the fibrin cover.

On account of the absence of the embryonic anlage the stage of development
cannot be accurately determined; the measurements are not sufficient for this
purpose, since, as has been pointed out, the contents of the ovum were shrunken
and the blood lacunae enormously distended. The relatively scanty growth of the
trophoblast may indicate, as Bryce and Teacher remark, that the ovum was younger
than that of Peters; the small size of the opening in the capsularis may also have
the same significance (see below, p. 117). However, definite conclusions cannot
be drawn from the preparation.

The ovum described by Stolper (1906) seems to represent a very young stage,
but it had evidently died some time before its abortion. The diameters of the egg
capsule (2.5 X 2.2 X 1-0 mm.) are, at all events, smaller than in the two ova to be
described next, but for which the corresponding measurements are not given.
The embryo was macerated. The ovum is characterized by a very extensive develop-
ment of syncytium. Wide blood spaces, probably intended for a diminution of
the blood pressure in the communicating vessels, are regularly arranged around the
inten'illous space.

The results obtained by Graf Spee (1905) from a young ovum studied by
him have been stated only briefly, and until a thorough study of the ovum and
figures are available, a comparison with the ova already mentioned cannot be
made. The ovum was obtained from a case of oxalic acid poisoning; the mucous
membrane of the uterus " showed the areas, di\'ided by furrows, that are character-
istic of pregnancy," and in one of these at a point marked by a slight depression
of the surface was the ovum. " Beneath about two-thirds of the free surface of
the prominent area of mucous membrane, imbedded in a cavity in the inter-
glandular connective tissue of the uterine mucosa, was an ovum measuring 1.5 X 2.5
mm. in its greater diameters, poorly provided with villi, and with very small
embryonic structures in the anterior. Between the surface of the chorion and
the uterine tissue were here and there small quantities of blood from open blood-
vessels. The walls of the egg chamber consist throughout of elements of the
interglandular connective tissue of the uterus. The lumina of all the glands
open into the uterine lumen; none into the egg chamber. The portion of the
mucous membrane (serotina) intervening between the ovum and the muscularis
holds a large mass of blood (just as in the ovum of Peters) contained in enormously
enlarged endothelial canals and apparently stagnant even in life ; it may very well
have furnished nutrition to the ovum and at the same time have served as a
rampart protecting the parts of the mucous membrane near the muscularis from
the destructive contact action of the ovum. The walls of the egg chamber,
separating the ovum from the lumen of the uterus, consisted of a thicker or thinner
layer of the interglandular connective tissue next the ovum "and a single-layered
epithelial covering next the uterine ca\nty. Only in the region of the surface

Vol. I.— 8

114 HUMAN EMBRYOLOGY.

depression is the uterine tissue interrupted by an opening; which may be regarded
as the point of entrance of the ovum iato the uterine mucous membrane, the
implantation opening; it is closed only by a flat expanded blood-clot (fibrin with
enclosed leucocytes and red blood-corpuscles). The conditions are, accordingly,
very similar to those occurring in the human ovum described by Peters.

'^ The implantation opening, at this stage 0.8 mm. in diameter at the most,
has probably increased somewhat in size from what it was when first produced
by the ovum by stretching and growth, and perhaps also by histolysis of the
chamber wall, for I imagine that the ovum during the seven days which probably
intervene between fertilization and implantation cannot have increased much in
diameter and therefore cannot have measured much over 0.2 mm."

Among these data the most striking are the small amount of blood in the
immediate neighborhood of the ovum and the small number of villi. Nothing is
stated concerning the character of the chorionic epithelium, the syncytium, and
the intervillous space. The ovmn, nevertheless, does possess villi and in this
respect is further developed than Peters's preparation. It is questionable, how-
ever, if it is to be regarded as quite normal.

The ovum described by Jung agrees excellently in its general character with
that of Peters. It was obtained from a curetting, and, completely surrounded with
mucous membrane, was preserved, while still fresh, in 80 per cent, alcohol. Its age
was not determined.

The egg capsule was completely separated from the lumen of the uterus,
but was situated somewhat superficially. The somewhat compressed but uninjured
cap of the ovum was composed of coagulated blood and tufts of fibrin, together
with numerous leucocytes and degenerating decidua cells, and passed gradually
over into the transition zone. The diameter of this necrotic cap was 1.7 mm.;
it corresponds, according to the opinion of the author, to the closing coagulum
of other ova and its extent indicates that of the distended implantation opening.**
The diameter of the ovum exclusive of the chorionic epithelium was 2.5 X 2.2

(X1.1) mm.

The mesoderm of the chorion had already sent processes, the mesodermal axes
of the villi, into the extensively developed trophoblast (Jung avoids the use of
the term trophoblast and speaks only of ectoblast). The ovum was completely
surrounded by rudiments of vilH, all of about the same length; and on the
chorion membrane and at the roots of the villi was an epithelium, consisting of
two layers, a basal and a covering layer. The basal layer, composed of distinctly
defined cells, passed over into stout columns of cells, which frequently united and
so formed the shell around the ovum. Only occasionally did free cell-columns
occur, the representatives of free villi. In the peripheral portions the individual
cells were somewhat larger and clearer, but everywhere abundant mitoses could
be observed and there were no signs of degeneration in the peripheral elements.
Individual mitoses were so placed that one of the daughter cells passed into the
covering layer, this, the syncytium, showing no mitoses although the nuclei were,
for the most part, well presented. The protoplasm of the covering layer presented,
in general, a foamy structure; prickle processes projected toward the intervillous
space, at least in certain places. Only at certain regions of the periphery was
the covering layer, which frequently streamed into the maternal tissues, in
degeneration and forming a symplasma syncytiale in Bonnet's sense, perhaps as
the result of the action of maternal leucocytes. The vacuoles of the covering
layer at places contained what seemed to be altered maternal blood, but everjrwhere

"In this case the capsularis would not actually be closed. The gradual
transition of the cap into the transition zone on the lateral portions of the ovum
seems to be opposed to Jung's view. It is possible that the capsularis had at
one time been complete, but was again undergoing degeneration.

DEVELOPMENT OF EGG MEMBRANES AND PLACENTA. 115

a continuity of the syncytium with the maternal tissues, that is to say, with endothe-
lium, was lacking. The boundary between the maternal and fetal tissues was almost
everywhere easily recognizable, with some difficulty only in the regions where
symplasma structures occurred.

Between the trophoblast columns, that is to say, the anlagen of the villi,
there was a very irregular intervillous space ; this was abundantly tilled with blood,
was in continuity with the maternal vascular system by means of gaps in the
sieve-like trophoblast shell, and was lined by maternal tissue (endothelium) only
in the neighborhood of these gaps. The communications with the maternal vessels
were always narrow and the circulation must have been very slow. In the tran-
sition zone, situated outside the trophoblast shell, degenerating maternal tissue
occurred, partly associated with the formation of symplasmata, but always with-
out signs of active proliferation; also no new formation of blood-vessels could
be found. Around the ovum was a strip of fibrin of varying thickness, produced
by degeneration of the maternal tissue (stroma, endothelium, gland epithelium).
Leucocytes occurred abundantly in the transition zone, but not in the fetal tissues.
The glands were frequently destroyed by the trophoblast, but appeared to with-
stand its attacks for a longer time than the rest of the decidua; none of them
opened into the intervillous space, but they took a curved course around the ovum.
External to the transition zone a separation of the compacta and spongiosa had
taken place. The former was oedematous, beset with numerous lymphocytes, and
its gland ducts were contorted; typical decidua cells and hemorrhages were want-
ing, although the glands frequently contained clotted blood. The representatives
of the later decidua cells showed numerous mitoses. No oedema occurred in the
spongiosa.

The ovum of Beneke was obtained from a curetting twenty-five days after
the omission of a menstrual period and was fixed in alcohol. It contained an
embryo measuring 1.86 mm. in length, and had a cavity of 4.2 X 2.2 X 1*2 mm.,
surrounded by a trophoblast measuring 0.4-1.0 mm. in thickness. " As regards
the structure of the trophoblast the author can only confirm in general the obser-
vations of Siegenbeek, Peters, Marchand, and others.** The syncytial giant cells
are throughout of fetal origin and symplasma formation is not recognizable. The
sjmcytia had encroached upon the endothelium of the decidual vessels and also
upon the epithelium of the glands; by the development of extensive clefts in
the interior of the giant cells the intervillous blood spaces are being formed.
Scattered giant cells with prickle processes occur in the chorionic connective tissues
of the investment of the oviun; they wander to a certain depth into the decidual
tissue, where they may be recognized by their characteristic nuclei and by con-
taining glycogen. The decidual cells, extensively swollen, take part in the formation
of the so-called transition zone to a greater extent than has been supposed by
Peters, for example. The closing * tissue plug ' which fills the opening in the
reflexa corresponds in general in its histological constituents, blood, fibrin, leucocytes,
etc., with what Peters has described."

The measurements of Siegenbeek's ovum (4.5 X ^-^ mm.) were not made
directly, since the ovum had been opened by a tear at one spot and was collapsed^
but were estimated from the perimeter. It was obtained from a woman who had
met an accidental death from burning; the entire uterus was preserved in
formalin fourteen hours after death. The ovum was completely covered with
villi, those on the basal surface being stronger than the peripheral ones, and
those about the equator of the ovum the strongest of all. Free villi occurred;
the majority were continued into cell columns (ectoblastic trabeculae), which united

"Disse, who has subsequently studied the specimen, regards the entire
trophoblast of the ovum as maternal tissue and also transfers this same inter-
pretation to the Peters ovum.

I

I

%

116 HUxMAN EMBRYOLOGY.

together peripherally and formed an ectoblast shell traversed by large and small
spaces, and varying in thickness in different regions. In general it was thicker
on its peripheral than on its basal side. The ectoblast cells situated near the
maternal tissue were larger than those having a more central position and frequently
showed degenerating nuclei, but mitoses occurred in all portions of the ectoblast
shell. The boundary between the fetal and maternal tissues was difficult to make
out in certain regions. The intervillous space was formed by blood-filled lacunie
which were lined only by cellular ectoblast or by syncytium; the endothelium
was also frequently wanting in the blood-vessels at their communication with the
intervillous space. In the space were very many leucocytes and perhaps also
special nucleated elements of the maternal blood. The syncytium was only to be
found in the region of the blood paths; it showed no prickle processes and no
cuticula on the side next the ectoblast. The derivation of the syncytium from
maternal tissues (endothelium, epithelium, or connective tissue) was excluded, but
its continuity with the cellular ectoblast could not be made out, so that the origin
of the tissue could not be determined.

The ovum lay in the compacta, whose basal portion had the same structure
as the capsularis (reflexa), except as regards the occurrence of glands. The
capsularis, for the most part, lacked an epithelium and contained in its interior
fibrin stria?. Basally there were greatly distended glands filled with blood; around
the periphery of the ovum the glands were arranged concentrically, and the
glandular epithelium did not fomi syncytia. Characteristic decidual cells were
nowhere present. A sharp separation of the compacta and spongiosa had not yet
occurred in the decidua vera; the compacta was (Edematous."

The ovum of Rossi Doria was obtained from an abortion. It was injured
by a tear and does not seem to have contained an ernbiyo. The egg membranes
were rather well presened. The theoretical considerations of the author will be
discussed in note 23. Frassi's ovum was obtained from an operation fourteen days
after the omission of a menstrual period; the unopened uterus was preserved in
formalin. The ovum of Friolet was also obtained from an operation and fixed
in the unopened uterus. Both ova already showed, for the most part, a two-
layered epithelium over the villi; a criticism of the observations made upon these
ova will follow in the resume.

The ova of Peters, Jung, Beneke, and Siegenbeek, with their extensive
development of the trophoblast, fonn a single harmonious group, which may be
derived from conditions such as Bryce and Teacher have described. To the
older stages, on the other hand, a natural and easy transition is formed by the
Siegenbeek ovum.

B. RESUME OF THE FIRST PROCESSES OF DEVELOPMENT UP TO THE

FORMATION OF THE VILLI AND THE APPEARANCE

OF THE INTERVILLOUS SPACE.

From the foregoing the course of the first stages of developn
ment may, with a good deal of certainty, be concluded. Especially
is this so with regard to the implantation of the ovum. Of the
types of implantation mentioned in the introduction the inter-
stitial is the only one that concerns us here; as in the guinea-pig,
so in the human species, the ovum penetrates like a parasite,
through an opening that it forms for itself, into the mucosa and

"The ovum has more recently been studied by Veil (1905) ; the author has
not been able to accept the idea of an active penetration of the ectoderm into the
maternal tissues.

DEVELOPMENT OF EGG MEMBRANES AND PLACENTA. 117

develops there (Berry Hart, Graf Spee, Von Herff, Peters ^^). It
must at this time be very small, since otherwise such a penetration
of the entire ovum could not be readily understood. The opening
in the surface of the mucous membrane had a diameter of 0.1 mm.
in the Bryce-Teacher ovum, in that of Leopold its margins were
in contact, in that of Peters its diameter was 1 mm., and in that of
Graf Spee 0.8 mm. It is probably enlarged very quickly by the
growth of the ovum, and the diameter of the ovum at the time of
implantation is probably about 0.2 mm. (Graf Spee). The forma-
tion of the mesoderm cannot have begun, and it is questionable if
at this time even the cavities of the ovum (the blastoccel, medullo-
amniotic cavity, cavity of the yolk sack) have appeared. The
ovum of the guinea-pig forms at the moment of implantation a
solid cell mass (Graf Spee). A marked growth of the ovum is
dependent on favorable conditions of nutrition, and these are
furnished only after implantation. The ovum does not undergo
implantation in a furrow,^^ but at any portion of the smooth
mucous membrane where perhaps a special thickening or an
extravasation of blood, which may serve as an embryotrophe,
facilitates implantation. The spot is usually on either the anterior
or posterior wall of the uterus, and determines the situation of the
placenta. The implantation usually occurs between two glands,
and the glands are later forced apart by the growth of the pene-
trated ovum, so that they bend around it in curves. Implantation
in a gland is not probable, since the diameter of the ovum is
always greater than that of the lumen of a gland. During the
implantation the superficial epithelium and connective tissue are
dissolved and probably serve the ovum as embryotrophe ; the solu-
tion of the maternal tissues may perhaps be produced by the action
of ferments secreted by the ovum, and to this Bryce and Teacher
refer the vacuolation of the sjTicytium seen in young stages. The
penetration of the ovum is not determined by gravity, since the
minuteness of the ovum places this out of the question and, further-
more, the implantation takes place just as often contrary to the

"Rossi Doria believes in a kind of combination of penetration and circum-
vallation, since the ovum observed by him projected, for the most part, beyond
the level of the mucous membrane. The ovum was, however, much too old to
settle the question. He had to do, apparently, with a superficially implanted ovum.

** The mucous membrane of the non-gravid uterus never shows, even at the
greatest development of the premenstrual swelling, a formation of furrows and
elevations (compare Hitschmann and Adler) ; consequently the idea, frequently
expressed, that the implantation takes place in a furrow, as in the hedgehog, fails.
The formation of furrows is actually a symptom of pregnancy (Graf Spee) and
as such may direct the attention to the possibility of a young pregnancy in
autopsies, at a time when the ovum itself can scarcely be recognized. The furrows
are not preformed, but are produced as foldings of the continually thickening
mucous membrane.

118 HUMAN EMBRYOLOGY.

direction of gravity as in accordance with it on either of the
opposite walls of the uterus. Nor can the action of an internal
pressure by the uterus (Pfannenstiel) be assumed, since the ovum
floats in a quantity of detritus which it produces and which cannot
flow away on account of the swelling of the mucous membrane, but
is rather increased in quantity by the flow of additional material
from neighboring tissue spaces. There remains then only the sup-
position of an active penetration on the part of the ovum which
may be due to an amoeboid activity of the superficial cell layers of
the trophoblast (Peters), in favor of which evidence has been
obtained within recent times. Indications of an active penetration
by the ovum have also been furnished by young tubal pregnancies
(Filth, Aschoff, and others), in which the ovum has completely
destroyed the thin mucous membrane and has penetrated into the
muscularis. The fact that the tube is open at one extremity is
ample evidence of the non-existence of an internal pressure which
could force the ovum into the muscularis. The duration of the
implantation process, which in the guinea-pig is about eight hours,
may be estimated at about one day in man (Graf Spee).

As to the behavior of the ovum before implantation we rely
solely on conjecture based on a comparison of what occurs in
animals. The fertilization of the ovum set free from its follicle
probably takes place, as a rule, in the pars ampullaris tubaB, to
which the spermatozoa penetrate and where they may remain
capable of fertilization for days or perhaps for weeks (see, for
example, His: ^^ Anatomic menschlicher Embryonen," vol. ii).
The fertilized ovum then wanders down the tube and through the
uterus until it reaches the place of implantation ; this movement is
a passive one on the part of the ovum, being caused by the action
of the cilia of the surface of the tube and uterus. During this
time the ovum loses its corona radiata ^® and zona pellucida, and
passes through the first stages of development, that is to say, the
segmentation; it obtains the necessary oxygen from the serum
which moistens the mucous membrane and perhaps employs the
secretions of the membrane as embryotrophe (p. 119). The passage
through the tube to the implantation region is by no means rapid;
even in the white mouse, where the distance to be traversed is very
short, it occupies five or six days (Sobotta, Melissenos), in the
guinea-pig seven days (Graf Spee), and in larger animals, such
as the cat, dog, pig, and sheep, from eight to ten days (Bonnet).
Taking into account the length of the human tube, the assumption
that the wandering of the human ovum occupies eight or ten days
is quite reasonable, notwithstanding that the human ovum is rela-
tively small and the rapidity of the wandering increases, in general,

"The theory of Hofmeier that the corona radiata is retained and becomes
transformed into the syncytium is of only historical interest.

DEVELOPMENT OF EGG MEMBRANES AND PLACENTA. 119

with the smallness of the ovum (Minot places the wandering period
at eight days, Graf Spee at seven days, Pfannenstiel at from five
to seven days, and Bryce and Teacher at seven days).

Of the various' phases of the menstrual cycle, the premenstrual
is the most important for implantation; at least so the study of
the phenomena of menstruation seems to indicate. The pre-
menstrual loosening of the tissues would favor the penetration of
the ovum, the secretion of the glands would serve as embryotrophe
until the completion of implantation, and the mucous membrane
of the uterus in the cases of Peters, Leopold, Jung, and Siegen-
beek resembles much more a premenstrual membrane than a
decidua. The connective- tissue cells are, in Peters 's case, for ex-
ample, less plainly altered toward the decidual condition than they
are normally immediately before the appearance of the menses,
and this even although the time of menstruation was several days
overdue.^® Indeed, even in older ova, such as that of Frassi,
typical decidual cells occur only in the neighborhood of the ovum ;
and among all the young ova a distinct decidual alteration is to be
found only in that of Bryce and Teacher. We must assume that
the implantation exercises an inhibiting effect on the premenstrual
changes, for otherwise menstruation would not be omitted during
pregnancy ; and the delaying of the decidual changes in the uterine
connective tissue may be regarded as the visible expression of this
inhibition. Yet a certain amount of time must be granted the
ovum for the development of this inhibitory action ; an ovum im-
planted immediately before menstruation may well be sacrificed
to this process; and such menstruations would then perhaps be
abundant in quantity. Normally (typically) therefore the im-
plantation must take place several days before the time for the
appearance of the menses, but whether two or five days previously
cannot at present be determined. Perhaps two days is too short
an interval to allow the inhibitory action to become efficient.

If the times required for the passage through the tube, the
implantation, and the inhibition of menstruation be added together,
it follows that the expulsion of the ovum from its follicle and its
fertilization must normally occur at a minimum of about from
eleven to fourteen days before the date of the expected menstru-
ation. But this entire interval has been almost always neglected in
gyna?co]o2:ical literature, in accordance with the tables established
by His, and the age of the ovum has been determined from the

**The decidual cells are in any event to be derived from the stroma cells
of the uterine mucous membrane, and the various older theories (derivation from
perivascular cells, the now almost forgotten " perithelia," or leucocytes, etc.) are
negligible. Concerning the mitoses observed by Jung in the preparatory stages of
the decidual cells it is to be remarked that they furnish an explanation of the
at first rapid increase of the decidua.

120 HUMAN EMBRYOLOGY.

estimated time of appearance of the omitted menstruation. Conse-
quently nearly always the age estimates have been too low by the
amount given above. The interval between implantation and the
beginning of the expected menstruation has been considered by
Peters and Leopold, for instance, but they neglected the time
required for the passage through the tube. If one reckons from
the moment of fertilization, the Peters ovum must have been at
least fourteen days old (and implanted for about five days).

Implantation may, however, be possible in other phases of the
menstrual cycle than the premenstrual, and it may be that the
stimulus arising from the ovum may also have the property of
accelerating the occurrence of the premenstrual changes. Per-
haps certain pathological phenomena may be associated with pre-
cocious implantation (see Grosser '*Lehrbuch'^).

The view stated here is, however, scarcely in agreement with
the age estimates that have so far been published of various young
human ova. Bryce and Teacher, on the basis of an analysis of
twelve cases, reach conclusions quite at variance with that given
above, — namely, that menstruation is actually without influence an
conception and implantation; that, indeed, the latter may take
place on the day immediately before or after the calculated date
for the first omitted menstruation; and that, accordingly, it is not
the implantation that is responsible for the inhibition of the ap-
proaching menstruation, but the fertilization which has already
taken place in the ampulla of the tube. These authors, however,
start with the assumptions that fertilization occurs, on the average,
twenty-four hours after coition, and, secondly, they base their
calculations on a series of aborted ova as well as upon some others
which were obtained by operative interference necessitated by
pathological conditions of the uterine mucous membrane. If one
considers, on the one hand, how much uncertainty exists regarding
the time relations of the processes of fertilization and, on the other
hand, the fact that only two cases of normal pregnancies termi-
nated by extrinsic causes (Peters, Reichert) occur in their tables,
it may seem venturesome to set aside as without significance the
relationship of the premenstrual mucous membrane to the decidua,
which is capable of being directly observed. Cases in which a
spontaneous abortion occurred or in which there was a catarrh
of the mucosa which called for curetting and which, if longer
continued, would have produced a spontaneous abortion, may, in-
deed, be associated with an implantation in an improperly prepared
mucous membrane. The occurrence of typical decidua in the
Bryce-Teacher ovum is strange when compared with other results
(see p. 119). But at all events these authors have rendered the
service of having thrown full light upon the obscurity which pre-
vails concerning the course of the phenomena under discussion.

DEVELOPMENT OF EGG MEMBRANES AND PLACENTA. 121

The normal period of ovulation is also still quite uncertain.
Ovulation may take place at any time ; the prevailing view is that
it coincides with menstruation ^^ ( see Nagel : ' ' Handbuch der
Physiologic"), while -\ncel and Villemin (1907), on the ground of
their observations of freshly ruptured follicles, suppose that it
occurs, on the average, twelve days before the beginning of men-
struation. The latter period is in excellent agreement with the
view that the premenstrual phenomena are preparations for preg-
nancy; this can hardly be said of the former one.

The ovum ceases its penetration in the decidua compactaj
the implantation opening is closed by the coagulation of the tissue
liuids exuding from the mucous membrane, and the product of
this coagulation is the closing coagulum (fungoid tissue, fibrin
cover) which occurs in a whole series of young ova (Peters, Leo-
pold, Beneke, Graf Spee) and, consequently, can hardly be re-
garded, as Pfannenstiel would wish, as an abnormal occurrence.
In the Bryce-Teacher ovum the coagulum is wanting and the
authors suppose that it is first formed after the ovum has increased
in size and the implantation opening enlarged. The implanted
ovum begins to grow rapidly and presses further into the mucous
membrane, so that it divides this into a superficial and a deep layer
(Fig. 101). The superficial layer becomes the covering of the
o\nim on the side toward the cavity of the uterus, it becomes the
decidua capsnlaris,^^ which at first bears the implantation opening,

"According to Leopold and Ravano (Archiv f. Gyn., vol. Ixzxiii, 1907)
ovulation coincides with menstruation in about two-thirds of the observed cases,
but in one-third of them it occurred quite independently of it ; conception is possible
at any time. The authors estimate the period of ovulation from the condition
of the corpus luteum; but this estimate must necessarily be uncertain, since, in
view of the uncertainty of the time of ovulation, a basis for a thorough knowledge
of the time required for the development of the corpus luteum is lacking. Also
the observations of H. Bab (Deutsch. med. Wochenschr., 1908) indicate that
impregnation, and consequently also ovulation, takes place some days before
menstruation; nevertheless, it is as yet hardly possible to draw conclusions as to
the time of impregnation from the size of the embryo, as this author does. Com-
pare, for instance, the data furnished by Bab concerning his first two cases with
those given by Tandler (Anat. Anz., vol. xxxi, 1907) concerning an almost equally
developed embryo. The discussion whether the ovum belongs to the first omitted
(Lowenhardt-Sigismund) or the last completed menstruation, a discussion in
which Bab declares himself in favor of the former idea, arises from the old notion
that ovulation and menstruation, on the one hand, and fertilization and implanta-
tion, on the other, coincide. The latter coincidence has been disproved ; the former
is improbable, or at least requires demonstration.

" The decidua capsularis is the decidua reflexa of the older terminology.
The latter name is an expression of the older theories (W. Hunter, Reichert)
of its origin, to the effect that the mucous membrane was reflected or curved over
the ovum and fused over it. Since, however, young stages are opposed to this
view and older ones show no conditions that cannot be explained as well or even
better as the results of interstitial implantation, this theory, which up to ten
years ago was the only prevailing one, is now regarded as disposed of.

122 HUM.VN EMBRYOLOGY.

but later completely closes (see below). The deep layer, or what
remains of it, forms the basis of the later placenta and is the
decidua basalis (the decidua serotina of the older nomenclature) ;
lateral to the ovum is the decidua marginalis, whose fate is of
great importance for the later stages of development. The re-
maining mucous membrane forms the decidua vera, recently very
appropriately termed the decidua parietaiis by Bonnet.

Fic. lOl-'-PrrEnancy of the first montli. The ovum Fxpellfd with the entirededdiu; tbideddiu
■cBpsulariB sad chonon hnva been cut Ihrough and the intervillouji apace and extn-embryonic body-cavitjr
opened. Ch,, thoi'mn; D:., decidua caps ularis^ Dp., decidua parietaiis; £., embryo in amnion. X 11-

There are four structures that still require thorough discus-
sion : the trophoblast shell, the syncytium, the blood lacunae, and
tlie transition zone.

The tropiiohlast shell is to-day regarded unanimously, if we
neglect Pisse's view, as embryonic ectodermal tissue, as tropho-
blast (cytotrophoblast, trophoderm).** To it is also generally
ascribed the power of dissolving and absorbing the maternal tis-

" The view advanped at one time by Lanp'hans, but since relinquished, that
the layer of separiite cells upon the surfaces of the villi, arising' from the tropho-
blast, was derived from the fetal mesoderm and that only the syneytium corre-
sponded to the chorionic ectoderm has recently (on the last occasion in 1904) been
revived by Van der Hoeven, but without sufficient evidence.

DEVELOPMENT OP EGG MEMBRANES AND PLACENTA. 123

sues. Also analogies for the fact that it surrounds the ovum as
an extensive growth are to be found among animals, namely, in
the hedgehog.^^ That during its growth toward the maternal
tissues portions of the trophoblast also are destroyed,®^ and that a
zone of mutual penetration by the tissues, a transition zone, occurs,
are also phenomena frequently to be observed in animals. The
trophoblast shell usually develops more extensively on the basal
side of the ovum, where the nutrition is best (Peters), and there,
for the same reason, are formed the embryonic anlage and, later,
the placenta ^^ (Von Franque, Peters).

The syncytium and the hlood lacunce are associated topograph-
ically and perhaps genetically also. The former has been the
most disputed tissue in the whole field of histology, and even
to-day it is not yet thoroughly understood. Of the different
opinions as to its origin that have been advanced from time to time
only two need further consideration ; ^^ the one derives the syncyt-

** The investigation of the hedgehog we owe to Hiibrecht and his school.
In the literature only the first work on this animal^ that by Hubrecht himself
(1890), is generally known. According to this certain important differences exist
between the hedgehog and man, but more recent observations made by Resink imder
Hubrecht's direction (1903) have corrected a number of inaccuracies and thereby
revealed a greater resemblance to the hvunan conditions. For instance, the tissue
formerly termed the trophospongia and derived from the decidua is now assigned
to the trophoblast. (See also Grosser: Lehrbuch.)

" Jung, in agreement with Langhans, will not admit, at least in young stages,
the occurrence of a destruction of the peripheral portions of the trophoblast
shell, described especially by Peters. This author's results are regarded as post-
mortem phenomena.

*■ This superiority of the basal growth is not always pronounced ; apart from
the Bryce-Teacher ovum, which showed an especially strong equatorial development
of the syncytium, there was in the Jung oviun an almost equal development of
the trophoblast shell, in the Spee ovum villi occurred on the peripheral surface,
and in the Siegenbeek ovum there was again a superiority in the equatorial villi.
A purely equatorial villous girdle, such as the frequently figured Reichert ovum
(1873) showed, cannot be regarded as normal, since it can hardly be reconciled
with the idea of inter^itial implantation. The occurrence of variations within
certain limits is, however, not unthinkable, since they may be produced by factors
extrinsic to the ovum, such as the distribution of the embryotrophe, local pathologi-
cal changes in the mucous membrane, etc.

" So long as the mechanism of implantation was unexplained, speculation
concerning the origin of the syncytium had free rein. The early view, supported
by the most prominent investigators (Langhans and his school, Strahl) and which
a*ssigned its origin to the uterine epithelium, is irreconcilable with interstitial
implantation. Also the glandular epithelium need hardly now be considered as
a possible source. For a consideration of the early views consult, for example, the
well-known account of Waldeyer, also Peters and Strahl. Directly opposed to
the idea of its origin from the uterine epithelium are cases of pathological im-
plantation, such as are seen in ovarian pregnancies, for in these the villi have
a typical syncytial covering.

124 HUMAN EMBRYOLOGY.

iuin from the trophoblast, the other from the endothelium of the
maternal vessels.^^

The trophoblastic origin of the sjTicytium is upheld by all
supporters of Hubreeht's views and especially by all recent stu-
dents of the problem. The Bryce-Teacher ovum is especially
illuminating in this connection : in it a connection of the syncyt-
ium with the cytotrophoblast is, on the one hand, clear; and, on the
other hand, an anchoring of the ovum to the maternal tissues, that
is to say, a direct contact of syncytium and decidua, is wanting.
Peters, Leopold, and Jung expressly mention the occurrence in
their preparations of gradual transitions between the cytotropho-
blast and the syncytium (for example, the passage of nuclei from
the former into the latter, Jung) and the absence of similar tran-
sitions between the svncvtium and the endothelium. These facts
overthrow the opposed view of Pfannenstiel, based upon older
preparations, which view brings him into accord with a number of
older authors and for support of which he relies upon one uterine
ovum which he himself investigated and one tubal ovum; at the
same time other authors, such as Frassi and Bonnet, find no sup-
port from older ova for an origin of the syncytium from the
endothelium, but declare themselves in favor of its fetal origin.
The figures given by Pfannenstiel, which seem to speak for a
derivation of the syncytium from the endothelium, are, apparently,
capable of another interpretation (Frassi).

But although the fetal origin of the syncytium is no longer
doubtful, the beginning of its formation has not yet been sufficiently
studied. Hubrecht, Marchand, Bonnet, and others suppose that
the syncytium is the expression of a special vital energy and is
produced by the penetration of the trophoblast into the maternal
tissues. Peters, however, is of the opinion that the syncytium is
formed from the cytotrophoblast by a kind of degeneration process
influenced by tlie maternal blood. The syncytium of both the
Bryce-Teacher and the Peters ovum ^^ is undoubtedly materially
different from that of later stages, which forms a layer of almost
even thickness over the chorionic villi. In the Bryce-Teacher
o\nim there is a thick spongy syncytium shell resting upon a thin
layer of cytotrophoblast; in the Peters preparation there is a
great quantity of cytotrophoblast and a very irregular distribution
of the syncytium. This forms often large masses, which frequently

** Graf Spee does not express himself definitely on the question, but from
the remarkable occurrence in one instance of a cuticle between the syncytium and
the cell layer he is rather inclined to accept a maternal origin for the syncytium,
deriving it eventually from the giant marrow cells of the mother. This idea is
no longer tenable.

" The author is greatly indebted to Professor Peters for permission to study
and make use of this valuable preparation.

DEVELOPMENT OP EGG MEJIBRA-NES AND PLACENTA. 125

project freely into tlie blood, and at many places are provided with
relatively few, but greatly enlarged, nuclei, so that, as Peters points
out, they give the idea not of a progressive but of a regressive form
of tissue and according to Bonnet's terminology deserve to be
termed syniplasmata (Figs. 99 and 102). Only at certain places
does the sjTicytium form a lining for the blood lacunie, so as to
recall well-known figures. In the Leopold o\Tim, on the other
hand, it has many more of the usual characters; still more pro-
nounced, perhaps, is this condition in the Jung ovum, in which
degenerating syncytium, termed symplasma syncytiale by the
author, can be observed only locally. Following a view similar to

Fio. 102.— A pnnion ot lh« tn>phoblB-<t shell of the Petera ovum. The ^yncylixm hH< h me!-h-1ikc sr-

that of Bryce and Teacher, and as.suming that their ovum was
quite normal, we may suppose that two generations, so to speak,
of syncytium are formed. The first is associated with tlie im-
plantation and with the intense histolysis which leads to tlie
formation of the cavity of the e^g capsule; it is represented
by the syncytial shell of the Bryce- Teacher ovum. Later this
syncytium degenerates, for the most part, and the cytotrophoblast
assumes largely the function of breaking down the decidua. In
this way the appearance of the sj-ncytlum of the Peters ovum may
be explained; as a matter of fact, one finds in this ovum in some
regions what is almost entirely degenerating sj-ncytium, and in
others a syncytial system of trabeculse with enclosed blood-contain-
ing lacunae, comparable to those of the Bryce- Teacher ovum (Fig.

126 HUMAN EMBRYOLOGY.

102). Also the absence of prickle processes on the syncytium of
both the youngest ova is perhaps referable to these conditions.
With the gradual development of a circulation in the blood lacunae
the syncytium — perhaps a new, second generation of it — assumes
the task of extracting nutrition from the blood stream. Then one
finds the syncytium almost exclusively in contact with the maternal
blood (Jung, Siegenbeek), and only later can one again perceive
an active penetration of the syncytium into the maternal tissues
(Voigt, 19(35, also in the formation of syncytial giant cells; see
p. 148). The absorbing syncytium then possesses prickle processes.

At all events the syncytium has one very important peculiar-
ity; it prevents, just like living vascular endothelium, a coagulation
of the blood in contact with it and so makes possible a circulation
of blood in the lacunae. Yet this peculiarity is assumed also by the
cytotrophoblast, at least at the time of the opening of the maternal
capillaries, since (as, for example, in the Peters ovum) this tissue
forms in part the boundaries of the lacunae. Hofbauer suggests
that the prevention of coagulation depends upon a layer of albu-
mose deposited on the syncytium.

As regards the formation of the hlood lacunce, Bryce and
Teacher are of the opinion that large vacuoles form in the syncyt-
ium, which at first contain a ferment destined for the solution of
the decidua, but later, when this is expelled, the cavities of the
vacuoles become filled with maternal blood. In this way the
sponge-like infiltration of the syncytium mantle with blood is ex-
plained. Peters supposes them to be formed by the blood stream-
ing out under pressure from the vessels opened by the trophoblast
and excavating for itself, as it were, channels in the trophoblast;
since, according to his views, contact with the blood determines the
formation of the syncytium, it is easy to understand why the cyto-
trophoblast remains uncovered by it only at a few places. How-
ever, an active separation of the trophoblast cells and a subsequent
filling of the lacunae so formed is possible, as Frassi points out,
and such an idea receives support from what occurs in animals
{e.g., in the rat). In the preparations of Peters and Leopold the
lacunae are gorged with blood, but this may be the result of the
mode of death, since in the Jung ovum the amount of blood is not
excessive; at all events blood is to be regarded as the normal
contents of the lacunae. They are the advance stages of the subse-
quent intervillous space, which may be defined as a vascular cavity
bounded by fetal elements but filled with circulating maternal
blood.^® The lacunae break up the trophoblast shell into indi-

" Remains of maternal tissue, as for example the peripheral endothelial walls
of the opened capillaries, occur only on the outer sides of the space; see also
Fig. 100.

DEVELOPMENT OF EGG MEMBRANES AND PLACENTA. 127

vidual trabeculae and cords, which give the entire chorion a villous
appearance and may be termed primary villL^'^

Concerning the transition zone the following may be said,
briefly : The name was first employed in connection with the human
ovum by Peters, being borrowed from the description of the proc-
esses occurring in the placentation of Carnivora (Strahl). In
early stages (Bryce-Teacher) the zone is wanting; the ovum forms
a place for itself by fermentative solution of the maternal tissues.^^
Only later, in association with the disappearance of thf^ syncytial
shell, already described (p. 125), does the phagocytic activity of
the trophoblast become pronounced, and the fetal cells penetrate
between the maternal ones and form the frequently incompre-
hensible complication that authors have described. In the tran-
sition zone fibrin^® also first appears. Bryce and Teacher de-
scribe a zone of coagulated, necrotic fibrin around their ovum ; in
Peters 's preparations actual fibrin is completely wanting ; only the
degenerating syncytium frequently resembles placental fibrin and
occurs frequently in striae near the transition zone. Such tran-
sitions of the syncytium into '^fibrin" are also described by
Marchand (1903) in young ova. Jung speaks of a distinct streak
of fibrin which he compares to the Nitabuch stria (see p. 151) ; but
in somewhat older stages such streaks are not typically present
(compare Frassi). Necroses of the transition zone occur at first,
accordingly, in rather variable amounts, and typical fibrin striae
probably occur only after the cessation of the phagocytic activity
of the trophoblast.

C. THE STAGES FROM THE APPEARANCE OF THE VILU TO

THEIR COMPLETE FORMATION.

With the development of the blood lacunae means are pro-
vided for the nutrition of the embryo from the maternal blood;
the purely embryotrophic stage gives place to a transition stage
that will lead to the haemotrophic stage. At the same time the
ovum undergoes a very considerable enlargement. The processes
occurring in the transition stage which require further considera-
tion are, chiefly, the mode of enlargement of the ^gg chamber, the
closure of the decidua capsularis, the further fate of the tropho-
blast shell, and the transformation of the blood lacunae into the
intervillous space, together with the formation of the secondary
villi which goes hand in hand with this.

The enlargement of the egg chamber is produced by two fac-

"As to the use of this term by other authors, see p. 130, note
•• Analogous are the early stages in the development of the egg chamber in,
for example, the guinea-pig (Graf Spee).

" Concerning the use of this term see p. 151 et seq.

128 HUJIAN EMBRYOLOGY.

tors, both of which are already recognizable in the youngest ova.
One is a dilation caused by the growtli of the ovum ; it finds expres-
sion in the curved course of the glands at the periphery of the
egg chamber. The other factor is the splitting up of the marginal
decidua, which shows itself even in the youngest ova in the growth
of the margins of the opening of implantation over the ovnni.
But this very splitting of the marginal decidua is a much disputed
point in the history of placentation and is intelligible only by
ascribing vital properties to the trophoblast. This continues to
penetrate into the maternal tissues, opens vessels and glands,
destroys portions of the glands entirely, and so divides them into
a portion i>ertaining to thedecidua basalis and a portion pertain-

°xtl

in of the

mantina

,fint

"n-Sl

Ih

d
'1

le lumen

of llie uie

ub: Dr.

-. til

viLli and

cell colli

Dc.

de.

id

60. (Fro

mFrwi,

1907. J

ia Rland diiecl«i
: tlie litems. To
villi; Zl.S., Mil

ing to the capsularis. And since with the extension of the tropho-
blast the intervillous space also enlarges, the luraina of the glands
open, at least temporarily, into the latter (Fig. 103) ; and, on the
other hand, before their complete destruction, remnants of their
epithelium are to be found in the wall of the space (Fig. 104).
Since the destruction of the maternal tissue may be due in later
stages to fermentative solution in addition to phagocytosis, the
openings in the walls of the glands, for example, need not neces-
sarily be filled up by penetrating masses of trophoblast, but the
mere juxtaposition of such masses may be sufficient for the solu-
tion of tlie wall of the gland. Such a condition is shown indis-
putably, as it would seem, by Frassi, The "opening of glands
into the intervillous space,*' as it was formerly described, has been
regarded by a number of authors (Gottschalk, Hofmeier) as most

DEVELOPMENT OP EGG MEMBRANES AND PLACENTA. 129

certain, but by others it has been just as definitely denied; its
occurrence has been advanced as evidence in support of the older
theory of implantation, according to which the ovum adhered
superficially to the mucous membrane and became surrounded by
a wall formed from the membrane (deeidua "reflexa"). Frassi
has been able several times to observe directly in serial sections the
lateral openings of the glands and their free communication with
the intervillous space which was thus effected (Fig. 103). Hof-
meier had already described similar conditions. By these open-

Fio. 104.— To the right, au epithalUI mtuunt (Bp.
lining 1mv«r (Al.) o( the wall of th« intervillous space. To tl
decidum (O.) with leucocyta (L.), X 300. (From FnuBi. I

jngs blood naturally passes from the intervillous space into the
lumina of the glands and may greatly distend them, and thus the
frequently repeated observation of greatly enlarged glands filled
with blood in the neighborhood of the ovum becomes intelligible.
The opening of the glands into the space is in any event a very
transitory condition, since the trophoblast, blood-clots, and desqua-
mation of the epith^elium soon close the openings and the glands
are then completely divided. But one always finds beneath the
ovum, in the deeidua basalis, large glands, usually filled with
blood, which have lost their terminal portions. The blood which
has filled them may in later stages serve as embryotrophe.

330 HUMAN EMBRTOtOGY.

Epithelial remnants in the wall of the intervillous space (Fig.
104) have also been frequently observed (for example, by His) ;
but they have usually been regarded as having been derived from
the surface epithelium of the uterus and have been accepted as
bearing on the implantation question in the same way as the
**open gland communications." Frassi has also made clear the
relations of these epithelia to the destroyed glands.

The decidua capsularis is completely closed in all ova older
than that of Beneke. This closure must be effected by growth
processes — either by the growth of tissue from the margins of the
implantation opening, or by the organization of the basal portion
of the closing coagulum, the protruding portion of this being
thrown off. In the Frassi ovum, for example, the capsularis
covers the entire ovum as a smooth, almost evenly thick layer. It
still possesses uterine epithelium in its marginal portions and in
patches even up to the upper pole, and glands occur at its margin ;
their occurrence over the summit is impossible from the mode of
development of the membrane. Fibrin, partly in streaks, occurs
throughout the whole extent of the capsularis, and most distinctly
at its summit ; but no trace of the implantation opening is visible
in later stages. In the majority of ova in this stage of develop-
ment there is at the summit a tissue rich in fibrin and poor in
cells or even entirely without cells; this is Reichert's scar (for
example, Hofmeier ; older ova of Leopold, Graf Spee, and Peters ;
also Pfannenstiel, Rossi Doria, Cova, etc.). The scar either de-
notes the complete, organic closure of the capsularis, or, what is
more probable, it is the first sign of what is later a complete
degeneration of the capsularis, which becomes more and more
stretched by the growing ovum, but is only very incompletely
nourished on account of its possessing no blood-vessels of its own.

The changes in the trophohlast shell which occur during the
first stages of development concern partly the arrangement of its
cell materials, partly the cells themselves. By the ingrowth of
connective tissue (chorionic mesoderm) into the trophoblast cords
— a process which has already begun in the Peters ovum — these
cords, which have previously been termed primary villi, become
transformed into secondary villi, the true chorionic villi. These
secondary villi are, therefore, preformed by the primary villi,
but soon show independent growth.^^ The trophoblast, whose

** The terms primary and secondary villi have been employed in the literature
variously and with a somewhat different sense from that given them above.
Marchand (1903) speaks of primary villi up to the tim'e of the penetration of
the fetal blood into the mesodermal axes of the villi ; Hitschmann and Lindenthal
(1902) and Pfannenstiel (1903), until the formation of the typical two-layered
epithelium. According to Hitschmann and Lindenthal the primary villi are
characterized by their power of active penetration.

DEVELOPMENT OP EGG MEMBRANES AND PLACENTA. 131

superficial layer is transformed into syncytium, becomes divided
and spread out over the villi, until there remains only a single
layer of distinct cells, over which is a layer of syncytium, also, as
a rule, with a single row of nuclei. Both layers together consti-
tute the epithelium of the villi. Very early the villi send out
lateral branches and assume a dendritic appearance. The blood
lacuna between them expand, unite together to a greater extent
than formerly, and completely surround the villous growths; the
lacunae thus become transformed into the intervillous space, which

cond mantb. D., deridiu; Fib„

continues to extend toward the ovum until at length its mesoderm
is covered only by a two-layered covering of epithelium. This
covering and the mesoderm of the chorion now form the chorionic
membrane or plate, which, as is characteristic for a placenta olli-
formis (p. 93), closes the intervillous space on the side towards
the ovum.

But the entire tropboblast is not used in the covering of the
villi. It also gives rise to the cell columns, the cell islands, and
the basal ectoderm (the covering layer).

132 HUMAN EMBRYOLOGY.

The cell columns (Fig. 105) are remains of the primary villi
into which the mesoderm has not yet penetrated, and they unite
the tips of the branches of the villi {the anchoring villi, in contrast
to the ends of the lateral branches, which float freely in the inter-
villous space, the free or absorbing villi) with the wall of the
intervillous space. They consist of cellular trophoblast with a
superficial layer of syncytium or with the covering layer to be
described later. At first they are of considerable length ; and since
they contain no connective tissue the fixation of the ovum is at first
a rather loose one, so that in an abortion or by the manipulation
of a preparation young ova may comparatively readily be sepa-
rated entire from the capsule (Fig. 106). It is principally from

Fio. 106.— Aborted oi

the cell columns that the activity of the trophoblast, the splitting
up of the decidua, proceeds. Yet the cell columns continually
diminish in length, the trophoblast is used up, and the mesodermic
stroma of the villi extends out to the outer wall of the intervillous
space. At the end of the second month the cell columns have
vanished, the villi are firmly anchored, an abortion produces a
separation of the decidua, and the splitting of the marginal
decidua has ceased (Hitschmann and Lindenthal).

The cell islands or cell nodes, also termed large-celled islands
(Figs. 107 and 108), are also masses of trophoblast which have
not been distributed over the villi (Langhans, Rossi Doria,
Schickele, etc.). They are, it is true, attached to the ends of the
villi, but otherwise lie free in the interWIlous space. The indi-

DEVELOPMENT OP EGG MEMBRANES AND PLACENTA. 133

134 HUMAN EMBRYOLOay.

vidual trophoblast cells are remarkable for their size and their
swollen appearance, and have on these accounts been frequently
taken for decidual cells; nevertheless, the occurrence of true
decidual islands is at least doubtful,*^ The occurrence of vascular
remains in the islands, which would determine their nature, has

Fia. m

.— IJaaiU ectwienn {*. E.) on Ih

ewii

of the iiitervilloUH

Hurl

phoblMt; .S-H..

syncytium; Z..villu.. X 200.

been described by Franque and Vassmer, but denied by Giese
(1905), their supposed presence being based on an error of ob-
servation. The derivatives of the trophoblast, syncytium and
"fibrin" (see pp. 151 et seq.), are of constant occurrence in the

"The so-called decidual columns (Deciduabalken, Ijeopold) will be discussed
later with the dei-idual pillars. Happe (1907), like Pfaunenstiel (1903) and
Webster (1906), regards the islands as formed prineipaily of trophoblast, but also
niaintaitis that they oontoiu decidual tlisue (more spindle-shaped eells, loosely con-
nected together and partly with a finely granular intercellular substance).

DEVELOPMENT OP EGG MEMBRANES AND PLACENTA. 135

islands, which disappear in the course of the first months, being
for the most part converted into "fibrin."

The "basal ectoderm" is a term apphed by Langhans and
his school to that portion of the trophoblast which occurs on the
outer wall of the intervillous space; in somewhat older ova it
there forms a stratified layer (Fig. 109) and is frequently retained
until the end of pregnancy, if not as a continuous stratum, at least
in masses of cells arranged in groups (Figs. 129-132). Its rela-
tions in younger stages, at the commencement of the formation of
a continuous intervillous space, have been studied by Frassi. In
such cases there is found upon the outer surface of the intervillous
space the "covering layer," a simple layer of cells, resting as an
almost continuous sheet upon the deeidua. "The nuclei of these

elements are larger and take the stain more deeply and regularly
(than the nuclei of the decidual cells). With strong magnification
a distinct diflference can be perceived between the endonuclear sub-
stance of such cells and that of the decidual cells," The covering
layer is everywhere one-layered in Frassi 's preparations; it is in
places separated from the deeidua by fibrin and is lacking only in
a few places. It occurs here and there between the cell columns or
forms an external covering for these (Fig. 110), Transitions into
deeidua are absolutely wanting, but, on the other hand, they occur
into the syncytium, so that the covering layer is of fetal origin.
The boundary between the fetal and the maternal elements
is not always easy of determination; assistance is rendered in this
connection, according to Frassi and Jung, by the leucocytes which
occur abundantly and are always to be found in the neighborhood
of the ovum. It would appear that they cannot pass beyond the

136 HUMAN EMBRYOLOGY.

boundary of the ovum, which penetrates like a parasite into the
mucous membrane, and consequently they make possible the de-
termination of that boundary.

The term transition zone indicates that the boundary is not
a sharp one. Bonnet (1904), in the cases of older ova (those
containing an embryo 3 mm. in length), preferred to speak of a
detritus zone between the chorionic villi and the decidua. In
association with it are symplasma formations of the decidual cells
and enlarged glands and in the lumen exudations of secretion,
blood, and leucocytes.

The intervillous space has also received different interpreta-
tions from different investigators. According to the older im-
plantation theory, which held that the ovum became attached to
the mucous membrane only superficially and that the uterine
epithelium was retained, transformed into syncytium, the space
was necessarily regarded as a portion of the cavity of the uterus
enclosed between the ovum and the surface of the uterus; the
occurrence of blood within it was only accidental, or, at most, a
regular phenomenon only in later stages of development, its place
being taken in young stages by a secretion of the mucous mem-
brane, a kind of uterine milk. As a matter of fact the space was
usually found to be empty in aborted ova (Fig. 107) and even in
those obtained by operation and observed in situ (Fig. 118). These
observations were taken as evidence opposed to a regulated cir-
culation in the intervillous space; and the condition occurring in
the Peters ovum, for instance, in which the lacunae were engorged
with blood, was explained as the result of the action of the poison
taken by the mother. Frassi, who also found the space empty
in his ovum, although open communications with maternal blood-
vessels could be determined at various places, rightly maintained,
on the contrary, the existence of a regulated circulation, and
pointed out that, after the inflow of blood had ceased as a result
of the cessation of the heart-beats of the mother or of the ligation
of the arteries during operation, an outflow of blood through the
veins was still quite possible and, furthermore, would be aided
by the final contractions of the uterine musculature. Such con-
tractions, indeed, occurring as they do, though to a lesser degree,
throughout the whole period of pregnancy, may form an important
accessory factor in promoting a circulation, which at the best must
be difficult and slow, through the very irregular space (Von
Herff).

The views of Pfannenstiel regarding the formation of the
intervillous space will be considered later (p. 167).

With the formation of the intervillous space and the gradual
disappearance of the trophoblast shell the ovum passes from the
embryotrophic into the haemotrophic phase of placentation.

DEVELOPMENT OF EGG MEMBRANES AND PLACENTA. 137

IV. THE FORMATION OF THE PLACENTA; RELATIONS OF THE
EMBRYONIC MEMBRANES UP TO THEIR MATURITY.

{Hcemotrophic Phase of Placentation.)

a. DIFFERENTIATION OF THE CHORION; CHORION L^VE. DECIDUA

FARIETALIS. AND CAPSULARIS.

At first the trophoblast shell completely surrounds the ovum
and villi are formed over the entire surface of the chorion; the
entire chorion is at first a chorion frondosum. As the ovum in-
creases in size and projects more and more beyond the general
level of the mucous membrane, the decidua capsularis, which
covers it and is only poorly supplied with nourishment, is gradu-
ally distended more and more, the circulation in the intervillous
space over the convexity of the ovum becomes more and more
difiBcult, and the villi on the surface directed toward the capsularis
finally atrophy, so that the convexity of the chorion l3ecomes
smooth, becomes a chorion Iceve, while the basal portion of the
chorion frondosum becomes the placenta fetalis.

According to the observations of Pfannenstiel (1903) ova of
the fourth week (from the cessation of menstruation) already
distinctly show a bare spot at the capsularis pole, and even at the
end of the second week this pole may be almost destitute of villi.
Ova of the second to the fourth week project beyond the general
level of the mucous membrane to very varying extents, either as
far as the equator or even further. This condition is referred by
Pfannenstiel to varying depths of implantation ; the shallower the
implantation the more the ovum later projects beyond the level of
the mucosa. The depth of the implantation, on its part, depends
upon the intensity of the original growth of the trophoblast and
its action on the maternal tissues. Concerning the relation which
probably obtains between the depth of the implantation and certain
abnormal forms of placenta (placenta marginata, reflexa, accreta)
see Grosser 's **Lehrbuch." The further fate of the chorion
Iseve will be considered in connection with that of the decidua
capsularis.

The decidua parietalis (vera), in accordance with its pre-
menstrual relations, is alreadv more or less distinctlv diflferenti-
ated into a pars compacta and a pars spongiosa at the time of
implantation.^^ The former is essentially the region of stroma
changes while the latter shows characteristic gland forms. But
both layers during the first weeks of pregnancy still present the

** Peters did not observe the compact layer and believed that it develops
later, and Siegenbeek notes the lack of a distinct boundary between the two ; never-
theless it must be remembered that in this respect variations occur also in the
premenstrual mucous membrane. In the Jung ovum the layers are separated.

138 HUMAN EMBRYOLOGY.

premenstrual type, in accordance with the inhibitory effect exer-
cised by the implanted ovum upon the changes of the mucous
membrane (p. 119) ; in the stages now under consideration (Fig.
Ill) they are differentiated.

The deeidua eompacta (Fig. 112), in addition to the straighter
terminal portions of the glands and greatly enlarged blood-vessels,
also- contains decidual cells, which are formed from stroma cells

by the continuation of the changes that are characteristic of the
end of the premenstrual stage. They are large, clear, vesicular
cells, as much as 50 n in diameter, and are round or, from mutual
pressure, polygonal, resembling epithelial or epithelioid cells. The
changes by which they are produced do not occur simultaneously
in all the stroma cells; and even at the height of the formation of
the deeidua one may find here and there stroma cells but slightly
altered and showing division and growth phenomena, so that
Marchand (1904) recognizes two types of decidual cells, large and
small. The mature (large) decidual cells show, at the most, only

DEVELOPMENT OF EGG MEMBRANES AND PLACENTA. 139

direct nuclear division (they contain frequently two nuclei and
indications of a cell boundary between the nuclei) and, as fully
differentiated cells, are capable of no further progressive or
n^gresaive development, ilany of them degenerate during the
second half of pregnancy and are disposed of by leucocytes; but
the majority are thrown off either during or after birth. After
the fourth month they all become smaller again and more spindle-

!.— DeUJI of Fig, III; the gi»ail duct tht.t iodinted by Dr.l.ia the decidum pBrieOlia

, 9 Kcond month. The (land contatos mcretioo and sroiuid il an typical decidual oells and

a few IsucocyMm. a 350.

shaped and are arranged parallel to the surface (Pfannenstiel).
According to Wederhake (1906), Unna plasma-cells also occur in
the decidua, and transitions between these and typical decidual
cells.

The significance of the formation of the decidual cells lies,
according to Marchand, in the storing up of glycogen;*" the ma-

"Drieasen (1007), who recently hafi aprain taken wp the older observations
of Lan^hflns on tlie oeeiiTTence of jrlycoeen in the <1eeidua, finds that substance
chiefly in tlie fflandiilar epithelium of the aponpirma ; it is not always recopnizable
in the decidual cells. In the second half of pregnonoy it sradiially disappears.

140 HUMAN EMBRYOLOGY.

jority of other authors see in their formation a provision against
the too intensive penetration of the ovum into the mucous mem-
brane, without furnishing suflBcient evidence for such a view. Ac-
cording to Marchand, spindle-shaped epithelial cells grow out as
wandering epithelial cells from the degenerating glands of the
compaeta into the stroma and may there fuse to form multi-
nucleated masses.

In the deeidua spongiosa are to he found at first the glands
of pregnancy, also characterized by the further development of
the premenstrual changes (Figs. 87 and 113), They are greatly

enlarged and tortuous, irregular in section, and filled with secre-
tion. The enlarged epithelium projects into the lumen in the
form of papillae borne upon small elevations of the stroma; it is
composed of high cylindrical cells, with clear marginal zones filled
with secretion. Between the glands are very small connective-
tissue septa with scattered decidual cells; only near the larger
vessels are the septa broader. After the second month the
epithelial papillse disappear and the cavities of the glands become
low and broad as a result of the stretching of Uie entire deeidua,
due to the increase in size of the uterus. The epithelial cells con-
tinue to grow broader and lower (Fig, 114) until, finally, they
resemble an endothelium and are lacking in places. The cavities
of the glands then appear as small, elongated clefts, with thin
inter\'ening walls, resembling in mass an empty venous plexus

DEVELOPMENT OP EGG MEMBRANES AND PLACENTA. 141

, 114. — ^The«8g membranw And uterine wall opposite the ptaoenta in the fourth moni
i9eagFig.130. (Embryr, 13'^ctn.iD vertex-bnechmeaaurenieiit.) .4..iunaion; CA.-S., c
I tissue; CA.-Z., degenerated rhorionic villi; Cimp., deciilu* psrietsliH campoctaand ca

Fio. lis.— Detail of Fig. 114. The dtgenerated villi of tlie rhoiioo Iseve in the fourth month (the

lionic epitlielium; Ck.-B., cliorionic cuunective liuuei Drc., decidua CBpsularia and parietalis compacts,
Kith leueooyte?. X 300.

(Fig. 117). The separation of the decidua in an abortion or at
birth can therefore take place easily in the apongiosa. Only the
deepest portions of the glands (the boundary layer of His), which
lie between the irregularities of the surface of the muscularis,

142 nUJL4N EMBRYOLOGY.

retain their cubical epithelium and form the starting point for the
post-partum regeneration of the mucous membrane.

The surface epithelium becomes flattened and loses its cilia
(according to Marchand) ; furthermore, fat globules are formed

in the cells and symplasmic formations occur, and toward the end
of the tliird month the epithelium has practically disappeared.
At the same time the cavity of the uterus, the perional space (the
space surrounding the ovum (v,<i;) : Webster), which has at thi.s
time only a potential existence, disappears as the capsularis comes

t»IieoUBly. Amn.. Bmnion; Ch.-B., chorionic connective lifsiw: Zic., itilermertiste Kme (chorionic epitli*-
lium, remMngof the villi, dec id ua capiularis, and decidus parietalia compaoU); D. ip.. decidim parielaii*
■ponsiOAa; Dr., glandular r^raai&s. >. 90-

into contact with the parietalis. The capsularis (Figs. 114 to
117), by stretching and by degeneration as well, has become greatly
reduced and its remains now fuse with the decidua parietalis. The
view that it remains recognizable as a streak of cells up to the
close of jjregnancy is probablj- based on an error, the chorionic

DEVELOPMENT OF EGG MEMBRANES AND PLACENTA. 143

epithelium being mistaken for it. The degeneration of the cap-
suiaris can be demonstrated beyond question in the region of the
internal os uteri, where its fusion with the decidua parietalis is
impossible. Even at the fourth month the eapsularis (Fig. 116)
consists in that region of only a very thin layer of flattened ele-
ments with some elongated clefts, probably remnants of the inter-
villous space. The chorion Iceve also shows extensive degenerative
changes. The epithelium of the villi disappears, their stroma
undergoes hyaline degeneration (Figs. 114 to 116), and between
the hyaline masses so formed one finds the detritus of cells and
leucocytes. At the summit of the ovum even these hyaline re-
mains of the villi vanish (Fig. 117), but they persist in the neigh-
borhood of the placenta. The epithelium of the chorionic mem-
brane itself is, however, usually recognizable in the mature egg
membranes; external to it is a zone of detritus with the remains
of the villi, the eapsularis, and the decidua parietalis compacta, in
which also hyaline degeneration, as well as fusion and destruction
of the cells, has occurred (Fig. 117). Still more externally are the
remains of the spongiosa, which at the close of pregnancy is re-
duced to a thickness of 1-2 mm., but which still contains remains
of the gland cavities. The fatty degeneration of the decidua
parietalis, which was formerly regarded as the rule, occurs at
most only in exceptional instances.

b. THE PLACENTA.

In the formation of the placenta the chorion frondosum and
the decidua basalis participate, the former constituting the
placenta fetalis and the latter the placenta materna.**

The placenta fetalis consists of the chorion plate and the
chorionic villi; both contain a mesodermal stroma 'and an ecto-
dermal (trophoblastic) epithelimn.

The stroma of the villi is at an early period distinctly fibrillar
and provided with fusiform cells in the principal stems and in the
chorion plate ; in the lateral branches it is at first formed of stellate
cells with wide intercellular spaces, but even in these portions it
soon assumes a fibrillar character. In the meshwork of the con-
nective tissue there frequently occur in young ova lymphocyte-like
structures and some especially large cells, with highly vacuolated
plasma and large nuclei (Fig. 119), to which Hofbauer has called
attention and which he brings into relation with the plasma cells.
Their significance is, however, still uncertain. The capillaries of

** This latter term has varied somewhat in its si^ificance. Kolliker terms
the entire basalis the placenta materna and divides it into a pars non cadnca seu fixoy
which corresponds to the spongry portion, and a pars caduca, which is expelled
at birth and is usually known as the basal plate. However, the latter alone is
frequently termed the placenta materna.

HDMAN EMBRYOLOGY.

Fio. lis. — Anlsgeof theplaoenta from the second month. From a ut«rur obtained
The embryo had a verl«x-breech length o( 28 mm. Tlie same ea« as ii shown in Figs, lli, im. ana lao.
rti.-P.. chorion plate; Or., glands: b.£.. ba-'al ectoderm; i/f.. anchorins villi; M., miUKnilarisuteri: m.A.,
maternal artety in a placental Mptum (decidual pillart; N. F., Nilabuch's fibrin slria; «. F.. Rohr's fibrin
-atria; Z.-J„ cell island. X IS.

the fetal vascular system lie, for the most part, near the surface of
the villi. According to Bonnet (1903) lymph-vessels also occur
in the stroma of the villi and can be followed to larger vessels in
the chorionic membrane. Nerves are not recognizable in the

DEVELOPMENT OF EGG MEMBRANES AND PLACENTA. 145

placenta (Bueura). Fossati has described a network of fibres,
characterized by special histological peculiarities, as occurring
around the chorionic vessels. In the stroma of the chorion plate
Vol. I.— 10

146 HUMAN EMBRYOLOGY.

Langhans has described a more superficial subchorial vascular
layer and a deeper fibrillar one, which shows no sharply defined
boundary from the ccelom. These layers become distinguishable
only at about the third month. Glycogen is found in young ova
chiefly in the connective tissue of the chorion plate and of the
larger villi {Happe, Driessen). (For further particulars concern-
ing the stroma of the villi see Happe, 1907; and regarding elastic
fibres consult Fuss, 1906.)

The form of the villi, which is determined largely by the
stroma, changes during pregnancy in that, on the one hand, the
branchings of the villi become continually more numerous and the
villous trees larger, and, on the other hand, the branches them-
selves become more slender and longer {Fig. 120); yet even in
the mature placenta variations in this respect occur. In each
villus one or two arteries occur and one or two somewhat stronger
veins, the two sets of vessels being connected by a capillary net-

DEVELOPMENT OF EGG MEMBRANES AND PLACENTA. 147

work lying immediately beneath the epithelium (Fig. 121). (Con-
cerning the form of the villi see Minot, 1889, and Happe, 1907.)
The chorionic epithelium, as has already been stated, is two-
layered after the formation of the villi (Fig. 129). The deeper
layer, which is composed of distinctly separated cells, is usually
named from its discoverer the Langhans layer, but is also termed
the cell layer. The superficial layer is termed simply syncytium
or also syncytial layer or covering layer.^^ The two layers
together form the diplotrophoblast of Hubrecht. As a rule, the
cells of the Langhans layer are arranged in contact with each other
in an epithelial manner, but frequently the syncytium extends
between the cells (Fig. 119) to the basement membrane of the
epithelium (Bonnet, 1903). As a result of this it appears in
places as if the cells were arranged in separate cell territories
enclosed in a ground substance and with a kind of capsule or
bounding layer. This condition is regarded as the rule by Happe
(1907) among recent authors. The syncytium generally forms a
layer of almost the same thickness as the cell layer and has but a
single layer of nuclei. Vacuoles, that are so striking in the
syncytium in early stages, are also to be seen at later periods and
may be the expression of degeneration or of the absorption of
material. On its outer surface it is provided with a delicate
membrane, which proves to be composed of prickle processes, stiff
hairs or rodlets, stereocilia (Graf Spee, Von Lenhossek, Bonnet).
This membrane is perhaps existent only under certain functional
conditions and cannot always be perceived ; the rudimentary basal
bodies described by Lenhossek as occurring in the cilia have not
been found again by Bonnet. Indications of absorption in the
form of fat globules, basophile granules, and mitochondria occur
in the syncytium, and it takes up haemoglobin in a soluble form.
On its outer surface it frequently bears irregular, multinuclear
elevations or buds (proliferation nodes; Fig. 122), which occa-
sionally become separated and may be carried in the circulation
far from the intervillous space (the deportation of syncytial ele-
ments of Veit). They are probably indications of amoeboid
activit)^ which, in all probability, occurs in the syncytium.*^ De-
generation (the formation of symplasma syncytiale with spiny
nuclei and the dissolving of the plasma into clouds or drops) may
be observed, according to Bonnet, in the syncytium in younger
stages; in older stages it takes on other forms (see p. 151).

*To the two layers of chorionic epithelium have been ascribed by different
investigators very various and somewhat remarkable significances. For a review
of the different origins suggested for the epithelium, which have been copied in a
number of papers, see Waldeyer, 1890.

**Also entire villi may be torn away by the blood stream and enter the
maternal vascular system.

148 HTJMAN EMBRYOLOGY.

Glycogen occurs in the cytotrophoblast (in the cell columns
and cell islands, less regularly in the Langhans cells) ; it is lacking
in the syncytium. It disappears completely with increasmg
maturity of the placenta (Driessen, Happe, 1907).

Mitoses occur only in the Langhans layer; in the syncytium
only direct division occurs, and it is rare (Van Cauwenberghe).
The direct passage of a cell from one layer into the other has not
yet been observetl in older stages and occurs only occasionally in
younger ones (see p. 114). Nevertheless, the distribution of the
nuclear divisions must be taken as evidence that even in later
stages the cell layer is the source of the syncytium and adds to

Sv.^p.

Fio. 122.— From ■ matun

pluenU (>fl«r Urth).

Formalin.

/.(?.. fetal chnrionio

vf>«l; «. B.

tonial blood^BrpUKles in th

syncytium

Sy.Sp; Byncytial p

roc™ (prolil-

tioD node). X 250.

it. The older opinion of Kastschenko, which has recently been
revived by Happe (1907), to the effect that the cell layer arises
from the syncytium, seeina to be overthrown by this. Between
the syncytium and the cell layer there is, according to Graf Spee
and Van Cauwenberghe, frequently but not regularly a cuticula
or deep syncytial membrane, which, however, is believed by most
other authors to be an artefact ; beneath the cell layer is a basement
or hyaline membrane. (For details concerning the epithelium of
the villi see Marchand, Friolet, Van Cauwenberghe, Happe.)

In addition to the occurrence of proliferation nodes there is
also another phenomenon that speaks in favor of amoeboid activi-
ties in the syncytium; this is the relation of the haftal (serotinal)
or syncytial giant cells (Figs. 123 and 124). In the decidua basalis

DEVELOPMENT OP EGG MEMBRANES AND PLACENTA. 149

one finds even in young stages multinucleated masses of proto-
plasm which cannot be distinguished histologically from syncytium
and are of great importance in connection with the significance
of the syncytium. In the Frassi ovum tliey are throughout {except
at one doubtful spot) in connection with the syncytium of the villi,
but in the preparations of J^eneke, Pfannenstiel, and Friolet, for
example, free masses of syncytium occur in the decidua basalis —
indeed, even in the superficial layers of the muscularis and fre-
quently in the neighborhood of vascular endothelium. They are
most frequent at about the middle of pregnancy, when they may
reach a very considerable size (Fig. 123) and may penetrate far
into the muscularis (Fig. 124); nevertheless their abundance is

Fio. 123.— Cisnt cells ber

. (hf fourth moi

Klolhelium of a vein of the i

muKle bundle.

A 300. From

« « fi«.. 130 and 131.

subject to rather great individual variations. Toward the end of
pregnancy they diminish in number. Pfannenstiel finds support, in
their occasional topographic relations to the vascular endothelium,
for the derivation of the entire syncytium from the endothelium;
but syncytial growths arising from endothelia are denied by
I'Molet and Frassi. Friolet leaves the possibility of their origin
from the connective tissue an open question; Pels Leusden, Web-
ster, Frassi, and others regard them as derivatives of the (fetal)
syncytium, that penetrate individually into the maternal tissues,*^

" That lliey may also penetrate toward tlie centre of the ovum is indirsted
at present only by the very definite statement of Beneke (p. 115). Sie^ibeek
also records the remarkable occurrence of a syncytium ma5is between the chorionic
epithelium and connective tissue, but considers it to have occurred by active
immigration into the o\Titn through a tear in its wall, which he assumes to have
occurred during life.

150 HUMAN EMBRYOLOGY.

and this view is certainly the most probable. The fact, also, that
they degenerate post partum, ■without taking any part in the
regeneration of the mucous membrane, is in favor of this view
(Wormaer).

Tia. 124.— PlMenU tn lilu (ram the seoond half of pn«oanoy. with numerom BUbplftomUl Byncyt-
inl gifiDt »Ub. D.b., dfciduB ba»»Lis; Dr., (Isads; Get,, msternal vea«ls; Hi., unchoring villi; MiMC., mu»-

Even in the fourth month the cell layer is present only in
patches, the syncytium resting, for the most part, directly on the
stroma of the villi. Toward the end of pregnancy individual
Langhans cells are still to be found beneath the syncytium, ac-
cording to Van Canwenberghe, yet this is certainly a by no means
frequent occurrence. The layer is partly spread out and stretched
over a constantly increasing area by the growth of the villi and is
partly used up in the formation of syncytium {Fig. 122). The

DEVELOPMENT OF EGG MEMBRANES AND PLACENTA. 151

syncytium also frequently shows signs of degeneration ; it becomes
greatly attenuated and may even be wanting at many places on
the surface of the villi. In such cases so-ealled placental fibrin
occurs on the villi.

This "fibrin" has also frequently been the object of investi-
gation and of controversy. In quite young ova (Peters, Leopold)
it does not occur; in older ones, in which the intervillous space
has formed, it first appears usually aa a stria situated some dis-
tance from the space in the basalis or even in the capsularis.

Chp.

Fio. ISG. — Chorion pl*te with aubehorisl eloai
plBcenM. Chp.. chorion piatfl; k. F., nnaliied fibrin;
Dcclive-UHue Btronu at desenerating villi, x SOl

The time of its appearance does not seem to be constant (see p.
127) ; but having once appeared it persists until the close of preg-
nancy. It was first described in a dissertation written by one of
Langhans' pupils and was named, from the authoress of the paper,
Nitabuch's fibrin stria. A second stria also occurs, though not
constantly, immediately in the wall of the intervillous space and
has been termed Rohr's stria*^ (Fig. 118). In addition, there is
a third stria which is constant in its occurrence close beneath the
chorion plate ; it appears, however, later, only in the second half
of pregnancy, and is known as Langhans' stria. In the same
region is to be found especially the "canalized fibrin" of Lang-
hans (Fig. 125), and, finally, quantities of fibrin occur everywhere

" Rohr himself names this the tipper stria, terming Nitabuch's the lower ttria.

152 HITMAN EMBRYOLOGY.

in the mature placenta and between the villi ; these fibrin masses
are, for the most part, microscopic in size, but frequently increase
to extensive structures. The small ones are termed fibrin nodes,
and the larger are known as white infarcts. The latter may occa-
sionally form almost half the mass of the placenta.

Langhans and his pupils regard the Nitabuch stria as marking
the boundary between the maternal and fetal tissues. It is certain

A smaU fibrin node b-

that it occurs in the transition zone and that the maternal tissues
that may be between it and the ovum quickly degenerate. Jung
derives the stria from the boundary zone of the maternal tissue
(see p. 115). It is at all events basal to tj^pical decidual tissues,
and is between the ovum and the basal ectoderm and degenerating
tissue, whose origin cannot always be certainly ascertained. It
is traversed by maternal (uteroplacental) vessels. That it is
practically the boundary between the mother and the ovum is also

DEVELOPMENT OF EGG MEMBRANES AND PLACENTA. 153

shown by its relations to the leucocytes; these, as* a rule, do not
pass beyond the stria. The fibrin of the Nitabuch stria is ap-
parently the first to appear in the placenta, yet the methods for
detecting the material in other portions of the placenta are insuf-
ficient. In general this so-called fibrin is by no means typical
blood-fibrin, it shows only occasionally the histological reactions
of fibrin. Hitschmann and Lindenthal believe that the fibrin
reaction is shown only at the commencement of its formation, and
that it later alters with age. It would be better, therefore, to
designate the substance by some indifferent term, such as fibrinoid
or fibrinoid substance. At all events, the stimulus for the forma-
tion of fibrinoid is afforded by degenerative changes, those occur-
ring in the decidua and chiefly in the region of the basalis being
responsible for the formation of the Nitabuch stria and the smaller
basal fibrin masses; yet the amount of participation of the indi-
vidual tissues of that region cannot as yet be strictly defined. At
other places the trophoblast must be regarded as the seat of the
fibrin formation; for very large quantities of fibrin are found
at places where the decidua is wanting, as, for instance, beneath
the chorion and between the villi. The maternal blood may also
participate, forming true fibrin; examples of this are shown in
places where the fibrin contains red and white blood-corpuscles.
It is also possible that the blood fibrin may become so altered in
course of time that it can no longer be detected by the usual histo-
chemical methods. It may be such fibrin that occurs' in the decidua
basalis and in the white infarcts, deposited as the result of the
disturbances in the circulation produced by the degeneration of
the epithelium of the villi and the fusion of these structures, or
as a result of the imperfect outflow of blood from the intervillous
space produced by villi being carried into the maternal veins, as
Giese suggests. The subchorial ** canalized fibrin" also presents
a peculiar layered structure (Fig. 125), which may be explained
as the result of the deposition of successive layers of blood fibrin,
especially since the blood stream is undoubtedly greatly retarded
in the roof of the intervillous space.**®

The derivation of fibrinoid from the trophoblast is based upon
the study of the formation of fibrin nodes on the villi; and it is
also supported by what can be seen in the formation of the Lang-
hans stria. In the villi one finds the first stages of fibrinoid forma-
tion partly between the syncytium and the connective-tissue
stroma, partly where the epithelium of the villi has almost dis-
appeared, as it does in every mature placenta. The occurrence
of the fibrinoid between the syncytium and the stroma points to the
cell layer as the seat of its formation, and this indication becomes

*Langhans spoke of tbe canalized fibrin as a tissue; but this conception of
it is incorrect, since it cannot be considered as living material.

154 HUMAN EMBRYOLOGY.

stronger in regions where the villi are closely packed together at
the time when the fibrin formation begins. One can then observe
how the formed masses of fibrin produce a cohesion of the villi and
how the Langhans cells occur between the fibrinoid and the stroma
of the villi ; also in the mature placenta the Langhans cells, prac-

tically wanting elsewhere, may be seen at the surface of the villi
(Fig. 127), usually in a continuous and sometimes in a double row;
and, furthermore, these cells occur free in the formed fibrinoid,
where they become vesicular in appearance and gradually lose
their staining properties, persisting for some time as "ghosts" of
their former selves and eventually becoming completely converted
into fibrinoid. The process of conversion cannot be termed a direct
necrosis of the cells; it has great similarity to what is seen in the

DEVELOPMENT OF EGG MEMBRANES AND PLACENTA. 155

formation of the matrix of many kinds of connective tissue, as,
for instance, when cells and even whole cell territories become
transformed into matrix in some kinds of cartilage. It is a
process apparently intermediate between secretion and the direct
transformation of the peripheral portions of the cells, and by the
continuation of it the entire cell becomes transformed. The
fibrinoid so formed lacks the property that inhibits coagulation
and that is possessed by the living epithelium of the villi, and so
the mass of the fibrin node is increased by the formation of fibrin
from the blood. Whether the syncytium also takes a direct part
in the formation of fibrinoid, or degenerates, or, perhaps, first
divides into separate cells which are then transformed into fibrin-
oid, has not yet been determined. The degenerating stroma of the
villi later undergoes a very similar (hyaline) transformation and
disappears in fibrinoid.

The chorion plate is the seat of formation of the Langhans
fibrin stria. In it even in the fourth month a partial transforma-
tion of the epithelium into fibrinoid can be detected, and in the
sixth month the epithelium in the middle of the placenta is replaced
by the fibrin stria. The lack of epithelium, on the one hand, and
the retarded blood flow, on the other, then produce blood coagula-
tion in layers, the result being canalized fibrin.

An important source of fibrinoid is to be found in the cell
islands, that are so frequent in the first month and later disappear.
In these also the beginning transformation into fibrinoid is evi-
dent very early (Fig. 108). Possibly these trophoblast masses
give a stimulus for the formation of the larger fibrin masses.

The description of fibrin formation given above resembles closely that given
by Schickele. The derivation of the fibrin from the trophoblast, in part at least,
has also been maintained, among others, by Kermauner, Hitschmann and Lindenthal,
and Giese. These authors advocate even more strongly than has been done above
the occurrence of disturbances in the circulation and the formation of fibrin from
the blood. Steffeck (1890) has derived all the fibrin from proliferated decidua,
a view that is to-day untenable; he has apparently throughout mistaken the
swollen degenerating trophoblast cells for decidua cells.

The transformation of the trophoblast may, however, be
carried even further and produce a liquefaction of the formed
fibrin; thus arise the placental cysts which are of very frequent
occurrence in mature placentae. Superficially situated cysts, oc-
curring in the Langhans stria, may reach the size of a hazel-nut
or even larger; more frequently are small microscopic cysts in
the middle of the tissues (Fig. 128). They are always enclosed
within a mantle of fibrinoid containing degenerating trophoblast
cells and are frequently lined by a flattened, endothelium-like layer
of these cells (Giese).

The white infarcts form, as the result of a combination of
fibrinoid and blood-fibrin formations, larger solid masses, which

156 HUMAN EMBRYOLOGY.

may enclose large villi, causing the degeneration and death of their
connective tissue, which eventually becomes imrecognizable as such.
The destruction of the connective tissue and chorionic vessels in
the infarct is, however, a secondary process, and not primary, as
Ackermann supposed, since the villi are nourished from the inter-
villous space and not by the chorionic vessels (see p. 164).

Eed infarcts, which are of much rarer occurrence and owe
their name to their color, are due to mass coagulation of the blood
in the intervillous space.

It is generally supposed that the cytotrophoblast, with the
exception of some scattered Langhans ceils lying beneath the
syncytium of the villi, has entirely disappeared in the mature
placenta; in speaking of the formation of fibrinoid, however, at-
tention has been called to the occurrence of isolated trophoblast
cells, and they are to be found rather constantly in two other
situations: in the floor of the intervillous space, their occurrence
in this region will be discussed in connection with the description of
the decidua basalis ; and in the region of the subchorial closing ring
(Waldeyer). In this region they form a cell plate of varying
breadth, circular, in correspondence to the margin of the placenta,

DEVELOPMENT OP EGG MEMBRANES AND PLACENTA. 157

and often wanting; when present, however, it lies between the
chorionic connective tissue and the Langhans fibrin stria, extends
inwards from the margin for about 1-2 cm. and laterally passes
over insensibly into the epithelial layer (p. 143} which persists on
the outer surface of the chorion laeve {Fig. 125). The closing ring
is the remains of the epithelium of the chorion plate, which further

Bp., bkjnl pLa-e: Chb.. Cht., chorionic connective tiuue sdiI epithdium belonsing (o tbe chorion iKve;
Chp.. chorion plalc; D. p., cjeciilua pariolalin (and capsuliris); Fib,, libria: I. G,. m. G., fetaJ and matenul
vesKle; /„ inFsTct: K., calareous deposit: ii. R.. iDlerviUoiu epux: f. Hr.. subchorisl cloMng nag. fre-
quently iaterrupleil: b. Tr., remejus of bual Irophoblaat: Z. I., villiu which travsrsei the Bubchm-inl
cloddA Hng^ 2i..coDnective-ti»ue stroma of viUi. K 17.

in has completely disappeared, that is to say, has become com-
pletely transformed into fibrinoid, and at the margin of the
placenta has, it is true, lost its syncytium and has formed fibrinoid,
but yet has largely persisted or has even become many-layered as
the result of proliferation. In these cells, even in the mature
placenta, the transformation into fibrinoid can be observed, and
the cell plate is usuallj' not continuous, but shows local defects
(Fig. 129).

158 HTIMAN EMBRYOLOGY.

Winkler originally described a continuous plate of cells as
existing beneath the connective tissue of the chorion plate, naming
it the closing plate and deriving it from the decidua. Kblliker
pointed out that a complete plate does not exist and speaks of a
decidua subchorialis occurring at the margin of the placenta, and
by this name the tissue is now generally known. Pfannenstiel
endeavors to explain it as produced by an undermining of the
marginal decidua by the marginal villi. The idea of a decidual
origin for the layer is based upon the pale and swollen appearance
of the cells, but this, as has already been several times noted, is

Fia. 130.— Margin of a placenta of the fourth month (vertex-brewh length of the embryo 13^^ cm.).
A decidua :<ubeboTiaLiB ip wanting. The glantt eavitieH of the ppongtosa (Dr.) liave been separalAl in
the preparation. Am.^ amnion; Ch.. choHon; b. E.. btuwd Qcloderm; 6. E. tF.). batiaJ eetodenn in procesa
□t traruifonnatiOD into Bbrinoid; Fib., fibrinoid; Mute., musculBriv; h: R., inlervilJouB i-pace; Zt.,
ceU nodes. X IS.

not a proof of its origin. Langhans in 1877 expressed doubts as
to the decidual nature of the layer and later (1891) decided in
favor of an ectodermal origin; Hitschmann and Lindenthal agree
with him in this. In the mature placenta the closing ring is occa-
sionally broken through by villi (Fig. 129), which are usually
atrophic and belong to the portion of the chorion which is
transitional between the chorion frondosum of the placenta and
tiie chorion Ifeve, and this fact is sufficient in itself to overthrow
the idea that one has to deal with an undermined marginal decidua.
There remains, therefore, for consideration only the assumption
of an active growth on the part of the decidua cells of the placental
margin towards the middle of the placenta, a supposition which
has little probability on account of what has already been said as

DEVELOPMENT OF EGG MEMBRANES AND PLACENTA. 159

to the degeneration of the decidua in the later stages of pregnancy.
But in addition this possibility is also excluded by the study of the
margin of the placenta in different months of pregnancy. This
shows {cf. Fig. 130) that the transition of the placenta into the
chorion laeve during the progress of pregnancy is a gradual one
and the two structures are first sharply marked out towards the
end of it. Normally a proliferation of the marginal decidua or
an undermining of it is never to be seen; but, on the other hand,
such preparations directly show the gradual degeneration of the
epithelium of the chorion plate in the middle of the placenta and its
transformation into the subchorial closing ring at its margin.

Perhaps a portion of this epithelium may persist throughout
the entire extent of the placenta, just as it does at its margin ; at
least this would explain cases such as that described by Steffeck,
in which an actually complete subchorial epithelial plate is said
to have been present, and which was identified by that author as
decidua. The conditions in a placenta marginata are quite dif-
ferent, for this may well owe its origin to an actual undermining
of the marginal decidua {cf. Pfannenstiel, 1903, and Grosser,
*'Lehrbuch'^).«^

The decidua hdsalis {placenta materna) is divisible in later
stages of pregnancy into a compact layer, the hasal plate of the
placenta, and a spongy layer. The former, which closes the inter-
villous space on the basal side, is formed from the portion of the
premenstrual compacta that is not destroyed by the ovum during
implantation; the latter is formed from the premenstrual
spongiosa. This shows (Figs. 118 and 124), in general, the same
changes as the decidua parietalis spongiosa; only the layer is
thinner, and the gland spaces appear to be less frequent, perhaps
because some of the glands, which in the early stages of the de-
velopment were filled with blood, have degenerated; between the
glands are the sjnicytial giant cells already mentioned. The basal
plate (Figs. 131 and 132) consists of decidua, which toward the end
of pregnancy again contains more fusiform cells, and also of the
fibrin stria* already described and of the remains of trophoblast
derived from the basal ectoderm and the cell columns of the
anchoring villi. These trophoblast remains, again, are partly
syncytial in character and partly appear as large, swollen, mono-
nuclear cells (mononuclear giant cells) similar to those found in
the early stages of fibrinoid formation in other places; these cells

80

Sfameni takes a different view of the origin of the placenta marginata. He
refers it to a lack or insufficiency of pressure within the ovum and to insufficient
stretching of the wall of the uterus. Compare also Kromer (1907) and Liepmann
(1906), as well as the polemic of these authors in Centralbl. f. Gynak., vol. xxxii,
1908.

160 HUMAN EMBETOLOGY.

lie, sometimes singly and sometimes in groups, in degenerating
tissue and in later stages may extend peripherally beyond the
Nitabuch stria. The trophoblast masses are no longer, however,
in direct connection with the anchoring villi ; the tips of the latter

tKe Nttabuch fibna etria ; Su, s

usually dip into masses of fibrinoid, which extend to the stroma
of the villi. Frequently this is more or less degenerated, as it is
in the infarcts.

In the basal plate there also occur the so-called choriodeddual
vessels (Euge). They are relatively large stems, visible to the
naked eye in the expelled placenta, provided that they are well

DEVELOPMENT OP EGG MEMBRANES AND PLACENTA. 161

filled with blood, or, better, injected from the vessels of the villi ;
they pass out from the villi, and either terminate in the basal plate
or enter the stem of a villus ascending from the basal plate. This
fact indicates that the villi concerned have come into contact with
the basal plate and have lost their epithelium and stroma by de-
generation, while their vessels have persisted and have become
enlarged by the blood-pressure, partly on account of degeneration
in their walls. Usually remains of trophoblast and of the stroma

Fig. 132. — Bbsa] plate of mUure expelled pluenta. Am.-ji.. arteria uUraplacea talis ; Db,
decidua baulis : Ep.. epithelial remaiiu in (be Qoor of tbt intervilloua Bpsw; Fib., fibrin; Hi., ancboring
villua: N. F>.. the Niubueh fibrin atria; Ri., monoDualeai liant cells (remains of tiophobUtill; Z>..
connective-tissue stroma ot villi endosed by fibrin. X TO.

of villi (Fig. 133) are to be found in the neighborhood of the ves-
sels, provided their entire surroundings have not been transformed
into a fibrinoid mass.

Kuge believed that his discovery of these vessels indicated
a vascularization of the decidua, that is, of maternal tissues, by
fetal vessels; the explanation' given above has already been advo-
cated by W. Wolska, working under Langhans' directions, and has
been confirmed by other authors. The statement, which has ap-
peared in some articles, to the effect that Huge has described an
anastomosis of fetal and maternal vessels, is erroneous.

From the basal plate there extend towards the intervillous
space the decidual pillars, which represent the septa placentiB of
later stages. The decidual pillars (Fig. 118) are to be regarded

Vol. I.— 11

162 HXJMAN EMBRYOLOGT.

as portions of the decidua basalis compacta which have been spared
during the penetration of the trophoblast. In structure they re-
semble the basal plate. As regards their number and arrange-
ment in young stages adequate investigations are as yet lacking.
Occasionally, but certainly not frequently, the pillars seem to
project for a considerable distance into the intervillous space, even
to near the chorion plate, and, in sections, appear to have no
connection with the basal plate, so that they seem to be "deeidua
islands" or decidual trabeculce (Leopold). (That free decidua
islands do not, in all probability, occur has already been noted.)
The septa placenfce in later stages and at the close of pregnancy
divide the placenta into separate lobes or cotyledons, which do not,

■n umbilicnl arMry iQ" =

imtun

eipglled plaetnte

Bp.. bual pUM: Fib.. Rbrin itnt.; G.,

v»«l<: ». «., inte^Uou.

Tr., baul dtgm-

annaetive-tiuu

e BtromB o( riUuB. X 40.

however, represent closed areas, since the septa in the middle of the
placenta are very low and even at the margin reach the chorion
plate only in small part. The original formation of these septa
from deeidua cells is almost always very difficult of determination
in the mature placenta (Fig. 134). The decidua cells have, for the
most part, degenerated and disappeared, and in their place there
remains only an empty mesh-work, into which the trophoblastic
anchoring villi penetrate. These frequently grow completely
through the septa, so that again fibrinoid formation and also the
inclusion of neighboring villi, together with their stroma, may be
found in the septa. Many septa at the close of pregnancy seem
to be composed entirely of fetal elements.

The basal plate is traversed by maternal or uteroplacental
vessels, destined for the intervillous space. Arteries and veins

DEVELOPMENT OP EGG MEMBRANES AND PLACENTA. 163

Fio. 134. — Saptum of » nutun eipdled pIsMnta. Tr,. trophoUut; Z., stroma of rilliu that hu foaed

with the Kptum. xao.

pass through the plate in sinuous courses, but at their entrance
into it they lose their muscularis and are represented by channels
lined only by endothelium. And even this is usually lost"' when

" The opinion of Waldeyer that the endotbelium is continued for some
distance upon the wall of the intervillous space, though in accordance with the
older views, has not been confirmed by later investigators.

164

HUMAN EMBRTOLOGT.

the vessels pass through the fibrin layers of the plate. The
arteries generally open in the region of the septa or close beside
them, while the veins arise rather towards the middle of the
cotyledons. This arrangement favors, to a certain extent, the
intervillous circulation. Both arteries and veins, as a rule,
traverse the wall of the intervillous space obliquely, yet villi are
frequently sucked into the veins or they may, as has already been
mentioned, be torn away and, passing into the veins, close them,
thus producing disturbances in the circulation.

— MArgiDiil portion of a mature pxpelled ptacentA vritli '
distendKl wilh ur. Ch.l,, chorion leve; D., trsgmenU of decidiu; up. (/.. uteroplaccDlaJ vesselt; K.,
flUperficial calcareoua depoHit; 0, opening into theroAricinalBiriuH (a tear, produced at birth by the divi^on
of A uterine vein), villi, which project into the margiaal sinua. beinc seen through the opening; Rt,^

Tbe conditions of the circulation in the placenta are quite peculiar and are
found nowhere else in llie body. The arteries open into a wide, very irregular
space, extending throughout tbe entire placenta and limited only by fetal elements
(and by flbrinoid). The space is formed from trophoblast laeunte and is filled with
blood by the erosion of maternal vessels; these at first are of merely capillary size
or but little greater. With the increasing importance of these afferent and efferent
veeeels they become graduaJly larger. Originally the opening of the vessels occurs
in the region of the transition zone, and even later the union of the vessels with
the intervillous space is still characterized by the fact that their endothelium has
no continuity with any of the cellular elements that line the space (syncytium,
basal ectoderm). The intervillous space is both the functional and the nutritive
vascular space of the placenta; from it the villi derii'e their nourishment, the
fetal circulation playing merely a subordinate role in this respect. Even after the
death of the embryo the placenta may persist for a considerable time and may
continue to grow, although only in an atypical n

DEVELOPMENT OP EQG MEMBRANES AND PLACENTA. 165

One of the efferent channels of the placenta is the marginal
sinus, Meckel's blood-channel, the sinus drcularis; it is situated in
the anj^le between the margin of the placenta and the chorion laevc

Fia. 13a.— M»r«in of the plaamU i

n the Meonci month, Fp

am the ume ase u Fig.

Chp.. charion plale: Par.

k; (;.-t., lumen ot the ut

Bnis. X15.

(Fig. 135), and does not encircle the entire placenta (it is wanting
at the region shown in Fig. 129), but only about one-quarter, or at
most seven-eighths, of the circumference (Budde) ; occasionally it
can scarcely be recognized. It is not to be regarded as a con-

166 HUMAN EMBRYOLOGY.

tinuous, regular vessel, but as a rather irregular apace of varying
diameter, which presents peripherally gaps and openings, cor-
responding to uterine veins that have been torn away; and gaps
of varying size also occur on its inner wall through which bunches
of villi project and by which it is in communication with the
intervillous space {Figs. 135 and 137). Budde agrees with earlier

Pia. 137.— Mursinal siaiu of K mstun eipeUed pluenta with sn sDdothelium-like lipiDi. Ch. I., Chorion

authors in regarding the entire sinus as the marginal portion of
the intervillous space, its inner wall, so far as it is formed, being
produced by cohesion of the marginal villi and by the formation
of fibrin. This explanation does not seem to suffice for all cases;
in younger ova greatly enlarged veins occur, which have a circular
course and have been regarded as the marginal sinus {e.g., by
Friolet and in the case shown in Fig. 136), and in the mature

DEVELOPMENT OF EGG MEMBRANES AND PLACENTA. 167

placenta a complete endothelium-like lining is occasionally found
in the sinus (Fig. 137). Nevertheless, this endothelium rests upon
a necrotic substratum resembling an infarct and containing de-
generating villi, and it is not impossible that the flat cells are
derived from the epithelium of villi ; the question, however, needs
further investigation.

The relations of the circulation in later stages are not essen-
tially different from those that obtain in younger ova; in the ma-
ture expelled placenta also the intervillous space is, as a rule, but
incompletely filled (Fig. 122) or almost empty (Fig. 129). Pla-
centae fixed in situ are usually gorged with blood (Bloch, 1889). The
circulation is determined, on the one hand, by the arrangement of
the uteroplacental vessels, already described, and on the other, by
the pregnancy pains already referred to (p. 136). The poverty in
blood of the expelled placenta is further evidence of a compara-
tively well-determined circulation.

In considering the growth of the placenta a distinction must
be made between growth in thickness and growth in area. The
growth in thickness is chiefly due to an elongation of the villi and
the associated separation of the chorion plate from the basal plate.

Somewhat different from this is the view of Pfannenstiel (1903). As has
already been pointed out, this author derives the syncytium from the endothelium
of the maternal blood-vessels and regards the first-formed blood lacunfle as greatly
enlarged capillaries; he terms them the primary intervillous space. This space
then enlarges by the veins which open on its floor and into which bunches of
villi project, enlarging as the result of a degeneration of their walls, this degen-
eration extending as far as the arteries which open between the veins; the tissue
surrounding the arteries, however, persists to form the decidual pillars, that is
to say, the septa placent«8. The new space so formed is termed the secondary
intervillous space. The projection of villi into the veins is incontestable (see p.
164) ; the process assumed to occur by Pfannenstiel cannot, however, have any
important significance, since, firstly, anchoring villi are at that time attached to
the basal plate in the neighborhood of the openings of the veins and their attach-
ment would be broken by such a degeneration, without the possibility of forming
a new attachment after the destruction of the cell columns. Secondly, the basal
plate is not thicker in the early stages of development than it is later, and such
a melting away of the portion of it that is in relation to the intervillous space
would require a very intensive proliferation of the decidua basalis for the replace-
ment of the lost layers. But there is no histological evidence of the occurrence of
such a proliferation.

The question of the growth in area of the placenta presents
great difficulties, apart from that which occurs during the embryo-
trophic stage of placentation. The most important factor in this
latter growth is the splitting of the marginal decidua, and the
occurrence of this process makes it intelligible how the ovum, at
first a mere dot but later increasing enormously in size, forms for
itself a capsule, which projects beyond the level of the mucous
membrane as far as the equator of the ovum or even beyond it

168 HUMAN EMBRYOLOGY.

and fills a considerable portion of the uterus. But the growth in
area of the placenta is not confined to the embryotrophic period;
the placenta reaches its greatest relative extent at about the fourth
month (Von Herff), at which time it occupies almost the half of
the inner surface of the uterus. At this time it is depressed in a
cup-like manner, at the centre, in correspondence with the almost
even curvature of the uterus. Later its growth is relatively less
rapid than that of the uterus and it becomes flatter in correspond-
ence with the stretching of the pregnant uterus and the slight
flattening of its anterior and posterior walls.

This, at first, rapid enlargement of the placenta has been re-
garded by Hitschmann and Lindenthal as the result of a gradual
inclusion in the placenta of the decidua capsularis and the portions
of the chorion frondosum opposite to it, there being at the same
time a stretching of the summit of the capsularis and of the chorion
loBve — in other words, it is due to a kind of unrolling and stretching
of the chorion frondosum; but no evidence tliat such a process
occurs is forthcoming. The possibility of a shifting of the margin
of the placenta, as a result of unequal growth, is also worthy of
consideration. Similarly, the later relative diminution of the
placenta may be due to two different causes; either there is a
degeneration of its marginal portions or there is again a shifting
of the margin as the result of unequal growth.

Pfannenstiel chiefly inclines toward a shifting of the margin,
which has, indeed, the greater probability ; yet the process cannot
be a simple one on account of the manifold connections between
the placenta and the subjacent tissues by means of the blood-ves-
sels. The decidua basalis spongiosa with its large gland cavities
forms, it is true, a very adaptable substratum. But an obliteration
of the marginal portions in later stages is also very probable, since
younger placentae (Fig. 130) show a relatively gradual transition
into the chorion laeve and only later does a distinct placental margin
appear. A solution of the problem may perhaps be obtained in
the following manner: Villi are probably formed only in early
stages by the ingrowth of mesoderm into the trophoblast shell
(Hitschmann and Lindenthal) ; after the formation of the chorion
plate and its two-layered epithelium the new-formation of villi
must cease. The destruction of smaller villi in the subchorial
fibrin stria is probable, but the larger ones must persist until the
mature placenta, in which, as a rule, a villus corresponds to each
cotyledon. An enumeration of the basally directed villi at dif-
ferent stages would show whether the placenta was enlarged by
taking into its territory new portions of the chorion and later
diminished by excluding them again, or whether a certain con-
stancy in the numbers occurred. Such enumerations have not,
however, as yet been attempted.

DEVELOPMENT OP EGG MEMBRANES AND PLACENTA. 169

The situation of the placenta, which is determined at implanta-
tion, is just as frequently upon the anterior as upon posterior wall
of the uterus ; more rarely it is lateral, in which case it may cover
the opening of a tube.^^ According to Holzapfel (1898), in 107
cases the placenta was situated on the anterior wall in forty-two,
on the posterior wall in forty-five ( both inclusive of cases of extra-
median positions and extension upon the fundus), in a tubal angle
in fourteen, laterally below the opening of a tube in five. One case
was a placenta praevia (covering the os internum uteri), but this
condition is of rare occurrence, since according to Schauta but one
case occurs in 1500-1600 pregnancies. It may result from a per-
sistence of a portion of the capsularis with its intervillous space
and supply of villi (placenta reflexa), or from an abnormally low
implantation of the ovum, near the ostium internum, or perhaps
from a double implantation on both walls of the uterus at the same
time, as has occasionally been observed (Graf Spee) in guinea-pigs
(Hitschmann and Lindenthal).

V. THE MATURE AFTERBIRTH; THE AMNION, ALLANTOIS AND

YOLK SACK UP TO MATURITY.

The immediate causes of birth are still unknown, yet it may be
said that in general the placenta is so altered at the close of preg-
nancy by the continued modifications of the epithelium of the villi,
the disappearance of the Langhans layer and syncytium, the forma-
tion of fibrinoid and infarcts, that it can no longer perform its
function of affording nourishment to the child, or can do so at
best only insufficiently. The trophoblast and sjTicytium have a
limited span of life and its close is reached with the close of
pregnancy.

The plane of separation of the afterbirth lies in the region of
the decidua spongiosa, in which preparations for it have been
made by anatomical conditions (the thin gland partitions) (Lang-
hans) ; nevertheless, local separations occur also in the compacta,
and, indeed, are regarded as the rule by Webster. The placenta,
chorion laeve, and decidua compacta possess a certain amount of
firmness and are actually separated from the spongiosa by any
diminution of the inner surface of the uterus ; the result of this is
the formation of a retroplacental hcematoma, which begins to be
formed at the first rupture of the vessels.

The expelled placenta is, as a rule, disk-shaped and has a
diameter of 16-20 cm., a thickness of 2i^^/^-3 cm., and an average
weight of something over 500 Gm. Variations are not rare in all
dimensions and do not stand in any accurate relation to the

" The covering of an opening of a tube is evidence in favor of the splitting
of the decidua marginalis during the growth of the ovum.

170 HUIVrAN EMBRYOLOGY.

development of the child. The maternal or outer surface (Fig.
135) after the removal of the adhering blood-clots appears dark
reddish gray, frequently with small, somewhat pale spots; is
divided by furrows into 15-20 irregular lobes (cotyledons) ; and is,
in general, rather smooth, except for occasional adhering shreds
of tissue (portions of the spongiosa). The paler spots correspond
to anchoring villi and the bunches of villi which surround them,
and the darker areas between them are caused by the blood of the
intervillous space; yet these differences of color are evident only
when the basal plate is relatively thin and the maternal blood has
been retained in considerable quantity. Furthermore, small white
scales (calcareous deposits), very variable in number, are usually
to be seen; they usually occur in fibrin nodes (Figs. 127 and 129)
and are usually near the basal plate. Larger white or yellowish
masses projecting above the general surface are caused by the
white infarcts. The uteroplacental vessels traverse the basal plate
usually as greatly contorted canals (Bumm, Klein) ; the veins have
a greater calibre and more delicate walls than the arteries. In
each cotyledon there are about two or three veins situated centrally
and from three to five peripheral arteries (see also p. 162). (Con-
cerning the visibility of the choriodecidual vessels see p. 160.)
The cotyledons are incompletely separated by the septa placentae,
which extend from the furrows of the outer surface and by
manipulation of the placenta, or even by birth-trauma, may be
readily separated into two layers, so that the furrows appear
markedly deepened.

The fetal inner surface is whitish, and at first is covered by
the amnion; after this is removed it is rather smooth, with the
fetal vessels projecting from the surface. A marking of the sur-
face, usually visible, consisting of paler spots on a darker back-
ground, is due to the same causes as the corresponding marking
of the outer surface, but is dependent, as regards its visibility,
on the thickness of the subchorial layer of fibrin. From the sur-
face project occasionally the placental cysts (p. 155) filled with a
clear fluid. On section the fresh placenta is dark red and shows
a spongy structure ; the septa as well as the basal plate are more
grayish-red.

The arrangement and size of the cotyledons are determined
chiefly by the chorionic villi. In general, each cotyledon corre-
sponds to a villus, which, with its branches, fills the cavity of the
cotyledon and is attached by numerous anchoring villi to the basal
plate and the septa. Close to the origin of the villus from the
chorion plate branches are ^iven ofiF, which divide immediately
beneath the plate and are frequently included in the Langhans
stria and the canalized fibrin. Small or rudimentarv villi occur
on the chorion plate only in the region of the placental margin.

DEVELOPMENT OP EGG MEMBRANES AND PLACENTA. 171

The chorion (chorion Iseve) forms with the placenta a sack,
■which is opened in the afterbirth by a sht, often irregular or
triradiate, and corresponding to the lower pole of the ovum. It
is a grayish- or yellowish-red, easily torn membrane, whose outer
surface is rough and has attached to it shreds of decidua and
blood-clots. Its microscopic structure, and also that of the
placenta at birth, has been described in Section IV.

Hyrtl describes in the chorion la-ve, close to the margin of the
placenta, occasionally occurring arteriovenous anastomoses be-
tween fetal placental vessels of the size of a needle or more. The
vessels which occurred in the chorion Ifeve when it still possessed
villi have complete!;' disappeared at birth, so that the membrane
is non-vascular; yet occasionally some weak stems occur in the
marginal parts of the mature membrane.

The amnion is fused with the placenta and chorion, but may
be separated from these as an independent, transparent, glistening

membrane. After its separation its outer surface, and also the
inner surface of the chorion, has a fibrillar appearance, as delicate
connective-tissue strands which connect the two membranes have
been torn by the separation. The amnion consists of a connective-
tissue stroma and a cubical or cylindrical epithelium, in which
Lonnberg finds fat granules of fre<|uent occurrence. Rarely (and
principally in the placental region) the epithelium presents irregu-
lar whitish growths, the amniotic inlli (Fig. 138) (Ahlfeld), struc-
tures which are of normal occurrence in ungulates. The epithelium
over them is many-layered and the cells undergo comification and
desquamation. Blood-vessels are wanting in the amnion.

The fusion of the amnion and chorion is secondarily pro-
duced by the disappearance of the extra-embryonic coelom towards
the end of the second month (Strahl), as the result of the rapid
growth of the amniotic sack. The amniotic epithelium is at first
quite low and endothelium-like, and becomes cubical only in the
second half of pregnancy (Hondi). (Compare also Figs. 96, 114,
and 117.) Granules appear in the cells after the third month and
Bond! also describes granules in the mature amnion that staiu
with neutral red. Stomata he could not find.

172 HUMAN EMBRYOLOGY.

The liquor amnii, whose quantity amounts to about a litre at
the end of pregnancy, is a secretion of the amniotic epithelium
(Mandl, Bondi, Kreidl and Mandl). The evacuations of the fetal
urinary bladder have no noteworthy significance in its production
(compare also Wargaftig, 1907).

The umbilical cord (funiculus umbilicalis) is a cord which
is usually twisted anti-clockwise (to the left) ; it is normally about
the same length as the child, but may be reduced almost to nothing
or may reach three times the normal length. The twisting depends
upon the unequal growth of the two umbilical arteries, and this
again is associated with the slight difference which exists in the
diameters of the two arteries from the beginning and with the
difference of blood-pressure in the arteries as a result of the dif-
ference in frictional resistance (Neugebauer). The embryo, which
floats freely in the amniotic fluid and is almost sustained by it, is
passively rotated as the result of the gradual twisting of the cord,
and local growths of the arteries produce the false nodes which
occur in this. The angle at which tlie cord is inserted into the
placenta varies between 0° and 90"" and is greatest in cases where
the insertion is central ; when the attachment is at an acute angle
there occurs between the cord and the placenta what is known as
Schultze's amniotic fold, produced by the incomplete apposition
of the amnion to the cord and placenta, owing to the persistence of
the yolk sack and its vessels.

Microscopically there may be distinguished upon the surface
of the cord the single-layered cubical or flattened amniotic epithe-
lium, in which, according to Koster, stomata occur ; the connective-
tissue layer of the amnion is not distinguishable as a separate
sheet. The stroma of the cord consists of a gelatinous tissue,
Wharton's jelly, which is characterized by possessing stellate cells,
resembling embryonic cells, a scanty development of fibrillae, and
wide intercellular spaces. At the periphery and in the neighbor-
hood of the vessels the tissue is arranged in concentric layers
(Fig. 139). The vessels, especially the arteries, show stout longi-
tudinal muscle-bundles beneath the circular musculature, and these,
when contracted, form strong projections which facilitate the com-
plete closure of the vessels when the cord is severed (Henneberg,
Bucura). Vasa vasorum can be distinctly injected in the veins,
according to Conner, and while they cannot be injected in the
arteries yet their origins can be distinguished when the arteries
are laid open. Nerves can be followed from the abdominal cavity
of the child only to the umbilicus or a short distance beyond it;
they do not occur in the free portion of the cord (Bucura).
Finally, remains of the allantoic duct occur in the mature cord.

The allantoic duct is, according to Lowy, still hollow through-
out its entire length in embryos with a greatest length of 8 mm.,

DEVELOPMENT OF EGG MEMBRANES AND PLACENTA. 173

but has a very variable diameter, and in embryos of 9 mm. its lumen
is partly obliterated toward the peripheral end, while in those of
14 mm. it is open only in a small portion of its extent and that
portion is irregularly expanded ; even in the fourth month remains
of the duct are still to be fonnd in the neighborhood of the embryo
with a lumen and cubical epithelium (Fig. 139) ; and in the mature
cord there are to be found occasional epithelial pearls and occa-
sionally coils and lateral outpouchings as remnants of the duct.

The yolk stalk becomes divided shortly after the closure of
the umbilicus. In the umbilical cord remains of it may be foimd

FiO. 139. — Central portion of a Irsaivenie wction o[ sn umbiliesi cord ol »n embryo of the fourth
moDth (vertex-bnecb leosth 13'-^ cm.). The WhartomBc jelly ia Bmniedin ooaoentrio layers. A. u,md
K.u., umbilioJvMKis: .lUir. sllaDtoicduct. Tbe yolk aUlk liudiMpiWMnl. X 30.

up to the third month, but at maturity these remnants have prob-
ably completely vanished. Portions of the omphalomesenteric
vessels, occasionally filled with blood, are also to be found in the
third month and, rarely, they persist until the close of pregnancy
(Lonnberg).

The yolk sack {vesicula urabilicalis) is a normal constituent
of the mature afterbirth (B. S. Sehultze), but on account of its
minuteness and the irregularity of its situation it is readily over-
looked. It occurs between the chorion and amnion, on the placenta
or the chorion la-ve, or even at the opposite pole of the ovum ; very
rarely it even appears to lie in the umbilical cord itself (Lonnberg).
Its variability in position is due to the length of the yolk stalk

174 HUMAN EMBRYOLOGY.

and the width of the exoccelom. The Schtdtze amniotic fold may
serve as a guide to it, but between the direction of the fold and
the connecting line between the sack and the umbilical cord there
may be a divergence of even 90° (Lonnberg). Maeroscopically the
mature yolk sack is usually a round or oval, flattened, white or
yellow body with a diameter of 1-5 mm. ; microscopically it presents
a mesodermal investment and its contents are flake-like and partly
calcified, but no epitiielium can be detected.

At the commencement of its development tlie yolk sack shows
a certain amount of differentiation. The blood and the vessels
of the ovum first appear in its wall and, later, for a considerable
time it is a region of blood formation and consequently richly
vascular (Fig. 140). Its epithelium forms gland-like invagina-

& hunuD embryo of s greatest lenith of 9 mm. Cy., inlra^pithdial
d-veeeel; Spl.. nplaDcbnopleure. X 300.

tions (Graf Spee) or intra-epitheliai cysts, produced by cell de-
generation (Fig. 140). (Compare also Branca.) Graf Spee also
describes the occurrence of giant cells in the epithelium of younger
stages and regards them as associated with the blood formation.
According to Meyer and Jordan there occur at the end of the first
month epithelial buds, solid or hollow outgrowths, which project
into the mesoderm, yet these structures are rather variable in
their occurrence. Later the epithelium becomes flat and, finally,
degenerates with the thickening up of the contents of the vesicle.

VI. THE UTERUS POST PARTUM,

Since the plane of separation of the afterbirth passes through
the decidua spongiosa, the numerous flattened gland cavities of
the latter are opened at birth. In the region of the placenta the
spongiosa is somewhat thinner than elsewhere (see p. 159). Hem-
orrhage from the opened vessels is prevented by the compression

PROPERTY OF

PCDI/Jf;»OS DEPT

HARVARD l^iLDlCAL SCHOOL

DEVELOPMENT OF EGG MEMBRANES AND PLACENTA. 175

of the vessels within the contracted muscularis and the compressed
mucosa, but blood-serum exudes for a considerable time from the
opened tissue spaces. The epithelium of the superficial gland
cavities, which Langhans believes is responsible for the renewal of
the superficial epithelium of the mucous membrane, has little sig-
nificance in this respect,^^ having undergone extensive modifica-
tions during pregnancy (p. 140). The regeneration is rather from
the deepest gland zone, the limiting layer of His ; but since this is
exposed only in spots, the more superficial layers of the spongiosa
and the persisting remains of the compacta must be destroyed by
coagulation necrosis and be expelled. Previously to their ex-
pulsion they form a whitish-yellow layer resting upon the mucous
membrane and have been usually regarded as necrosed compacta.
The line of demarcation between the necrotic and persisting
layers **is formed by the basal surfaces of all the gland cavities
occurring in its neighborhood, which thus later become the sur-
face" (of the mucosa) (Wormser). This line becomes distinct on
the second day after birth ; the expulsion of necrotic tissue begins
on the fifth day and is completed everywhere on the tenth to the
twelfth day after birth. The gaps between the gland cavities are
covered over after the expulsion *'by lateral shifting, flattening,
and amitotic increase" of the epithelium; mitoses seem to be at
first entirely wanting. As the epithelium grows out from the deeper
portions of the glands many-layered zones of epithelium and multi-
nuclear masses of protoplasm are formed, and, at the same time,
degenerations occur everywhere in the epithelium; the formation
of vacuoles, shrinkage of the nuclei, and degeneration of cells and
nuclei are frequently to be found at the surface. Mitoses first ap-
pear about two weeks after delivery, and, finally, probably only
those epithelial cells persist which have been newly formed by the
mitotic process. Leucocytes wander in rather large numbers
through the mucous membrane. The decidua cells degenerate in
the vicinity of the line of demarcation, probably by a fatty de-
generation; and the connective tissue scaffolding thus persists as
an empty mesh-work. This process Wormser terms areolar
degeneration, and he imagines the meshes to be eventually re-
occupied by inwandering connective- tissue cells; this idea, how-
ever, is rather improbable. The decidual modifications which
have occurred in the deeper layers of the mucous membrane disap-
pear, tiie syncytial giant cells degenerate and vanish, and in two
or three weeks after birth the regeneration of the mucous mem-
brane, accompanied by an increase in its thickness, is so far com-
pleted that stroma, tubular glands, and a surface epithelium are

*■ The account priven here is principally based on the obsen^ations of Wormser
(1906).

176 HUMAN EMBEYOLOGY.

already present; nevertheless, the epithelium continues to show
degenerations and regenerations for some time.

The mucous membrane of the cervix uteri becomes looser dur-
ing pregnancy and shows serous infiltration and an increase in the
glands, while after birth it presents zones of traumatic hemor-
rhages, the epithelium, however, being retained. Leucocytes also
wander out through this mucous membrane in considerable
numbers.

The muscularis uteri increases during pregnancy to about
twenty-four times its original size, partly by hypertrophy (the
formation of new fibres by the division of those already present)
and partly by hyperplasia of the individual fibres (Kolliker). The
reduction is produced by a diminution of the size of the fibres and
perhaps also by the complete degeneration of some of them (Von
Ebner).

The peritoneal covering of the uterus and of the parts in its
neighborhood shows here and there during pregnancy decidua-like
growths (Schmorl), and similar growths occur in the tunica
albuginea of the ovaries (Lindenthal). The tubes, with the excep-
tion of increased blood-supply and some serous infiltration, are but
little altered.

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Eihiillen, Zeitschr. f. Geb. u. Gyn., vol. xxxv, 1896, and vol. xxxvi, 1897.
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Ueber die Haftung des Eies an atypischem Orte, ibid,, 1903.
Der weisse Infarkt der Placenta, Archiv f. Gynak., vol. Ixix, 1903.
Hofbauer, T. : Grundziige einer Biologic der menschlichen Placenta mit besonderer

Beriicksichtigung der Fragen der fetalen Emahrung, Wien u. Leipzig, 1905

(literature).
Die menschliche Placenta als Assimilationsorgan, 1907.
Hopmeier, M. : Die menschliche Placenta, Wiesbaden, 1890.
HoLL, M. : Ueber die Blutgefasse der menschlichen Nachgeburt, Sitz-Ber. k. Akad.

Wiss., Wien, vol. Ixxxiii, 1881.
HoLSTi, O. N. : Weitere Beitrage zur Kenntnis der Embryotrophe, II. Ueber

die Fettzufuhr zum menschlichen Ei, Anat. Hefte, vol. xxxiii, 1908.
HoLZAPFEL, K. : Ueber den Placentarsitz, Beitrage z. Geburtsh. u. Gynak., vol. i,

1898.
Zur Pathologic der Eihaute, Beitr. zur Geburtsh. und Gynak., vol. viii, 1903.

(The author regards the amniotic villi as transplanted embryonic epidermis.)
Hyrtl, J. : Die Blutgefasse der menschlichen Nachgeburt in normalen und abnormen

Verbal tnissen, Wien, 1870.
IwASE, Y. : Ueber die zyklische Umwandlung der Uterusschleimhaut, Zeitschr. f.

Geburtsh. und Gynak., vol. Ixiii, 1908.
Jordan, H. E. : The Histology of the Yolk-sac of a 92-mm. Human Embryo, Anat.

Anzeiger, vol. xxxi, 1907.
Jung, Ph.: Beitrage zur fruhesten Ei-Einbettung beim menschlichen Weibe,

Berlin, 1908.

Vol. I.— 12

178 HUMAN EMBRYOLOGY.

BIastschenko, N.: Das menschliche Chorionepithel und dessen Rolle bei der

Histogenese der Placenta, Archiv f. Anat. u. Phys., Anat. Abt., 1885.
Kehrer, E. : Der placentare Stoffaustausch in seiner pbysiologischen und patho-

logischen Bedeutung, Wiirzburger AbhandL, vol. vii, parts 2 and 3, 1907

(literature).
Klein, G. : Mikroskopisches Verhalten der Uteroplacentargefasse, in Hofmeier:

Die menschlicbe Placenta, Wiesbaden, 1890.
Zur Entstehung der Placenta marginata und succenturiata, ibid.
KoLLMANN, J.: Kreislauf der Placenta, Chorionzotten und Telegonie, Zeitschr. f.

Biologie, vol. xlii, 1902.
Langhans, Th. : Zur Kenntnis der menschlichen Placenta, Archiv f. Gynak.,

vol. i, 1870.
Untersuchungen iiber die menschlicbe Placenta, Archiv f. Anat. u. Phys.,

Anat. Abt., 1877.
Ueber die Zellschicht des menschlichen Chorion, Festschr. f . Henle, Beitrage z.

Anat. u. Embryol., Bonn, 1882.
Syncytium und Zellschicht, Beitrage z. Geburtsh. u. Gynak., vol. v, 1901.
Leopold, G. : Uterus und Kind, mit Atlas, Leipzig, 1897.

Ueber ein sehr junges menschliches Ei in situ, Leipzig, 1906.
Leopold and Ravano : Neuer Beitrag zur Lehre von der Menstruation und Ovula-
tion, Archiv f. Gynak., vol. Ixxxiii, 1907.
LoNNBBRO, J. : Studien iiber das Nabelblaschen an der Nachgeburt des ausgetragenen

Kindes, Stockholm, 1901 (literature).
Mandl, L. : Histologische Untersuchungen iiber die sekretorische Tatigkeit des

Amnionepithels, Zeitschr. f. Greb. u. Gyn., vol. liv, 1905.
Weitere Beitrage zur Kenntnis der sekretorischen Tatigkeit des Amnionepithels,

ihid., vol. Iviii, 1906.
Marchand, F. : Beobachtungen an jungen menschlichen Eiem, Anat. Hefte, vol.

xxi, 1903.
Beitrag zur Kenntnis der normalen und pathologischen Histologic der Decidua,

Archiv f. Gynak., vol. Ixxii, 1904.
Mebttens, J.: Beitrage zur normalen and pathologischen Anatomie der mensch-
lichen Placenta, Zeitschr. f. Geb. u. Gyn., vol. xxx, 1894, and vol. xxxi, 1895.
Meyer, A. W. : On the Structure of the Human Umbilical Vesicle, Amer. Journal

of Anatomy, vol. iii, 1904.
MiNOT, Ch. S. : Uterus and Embryo, Journal of Morphology, vol. ii, 1889

(literature).
The Implantation of the Human Ovum in the Uterus, New York Med. Journ.,

vol. Ixxx, 1904.
Neugebauer, L. a. : Morphologic der menschlichen Nabelschnur, Breslau, 1858.
Nitabuch, R. : Beitrage zur Kenntnis der menschlichen Placenta, Dissert., Bern,

1887.
Peters, H. : Ueber die Einbettung des menschlichen Eies und das f riiheste bisher

bekannte menschliche Placentationsstadium, Leipzig and Wien, 1899

(literature).
Zum Kapitel: LanghansVhe Zellschicht, Zentralbl. f. Gyniik., 1900.
Beitrag zur Kasuistik der Vasa praevia und Gedanken zur Theorie der Insertio

velamentosa, Monatsschr. f. Geb. u. Gyniik., vol. xiii, 1901.
Pfannenstiel, J.: Die ersten Veranderungen der Gebarmutter infolge der

Schwangerschaft, — Die Einbettung des Eies, — Die Bildung der Placenta,

der Eihiiute und der Nabelschnur, — Die weiteren Veranderungen der

genannten Gebilde wahrend der Schwangerschaft, in Winckel: Handbuch

der Geburtshilfe, vol. i, Wiesbaden, 1903 (literature).
Reinstein-Mogilowa, a.: Ueber die Beteiligung der Zellschicht des Chorions an

der Bildung der Serotina und Refiexa, VirchoVs Archiv, vol. cxxiv, 1891.

DEVELOPMENT OF EGG MEMBRANES AND PLACENTA. 179

ROHBy K. : Die Beziehungen der miitterlichen Gefasse zu den intervillosen Raumen

der reifen Placenta, speziell zur Thrombose derselben (weisser Infarkt),

Virchow's Archiv, vol. cxv, 1889.
Rossi-DORIA, J.: Ueber die Einbettung des menschlichen Eies, studiert an einem

kleinen Ei der zweiten Woche, Archiv f , Gynak., voL Ixxvi, 1905.
RuGE, C. : Die Eihiillen des in der Geburt befindlichen Uterus, Bemerkungen iiber

den Ort und die Art der Emahrung des Kindes in demselben, in :
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Physiologic der GJeburtskunde, mit Atlas, Bonn, 1886.
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Beziehungen zur Entstehung der Cysten und Fibrinknoten der Placenta,

Beitr. z. Geb. u. Gyn., vol. x, 1905.
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der Physiologie, vol. ii, 1907.
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bettung, Verhandl. Deutsch. Gea f. Gynak., xi Meeting in Kiel, 1905,

Leipzig, 1906.
Steffeck, p.: Der weisse Infarkt der Placenta, in Hofmeier: Die menschliche

Placenta, Wiesbaden, 1890.
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Qeh, u. Gyn., vol. xxiv, 1906.
Strahl, H. : Die menschliche Placenta, Ergebnisse d. Anat. u. Entwickl., vol. ii,

1893 (literature).
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(literature).
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Einnistungsstelle j lingerer menschlicher Eier, Zeitschr. f. Geburtsh. u.

Gynak., vol. liv, 1905.
Waldeyer, W. : Ueber den Plaeentarkreislauf des Mensehen, Sitz.-Ber. k. preuss.

Akad. Wiss., 1887.
Bemerkungen iiber den Bau der Mensehen- und Affenplacenta, Archiv f. mikr.

Anat., vol. xxxv, 1890 (literature).
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Physiologie und Pathologie des Fniehtwassers, Diss., Freiburg, i. Br., 1907.
Webster, J. C. : Human Placentation, Chicago, 1901.

Die Placentation beim Mensehen, Transl. by Koliseher, Berlin, 1906.
Wederhake, J.: Ueber Plasma- und Deciduazellen, Monatsschr. f. Geburtsh. u.

Gynak., vol. xxiv, 1906.
WoLSKA, W.: Ueber die von Ruge beschriebene fetale Vaskularisation der Serotina,

Dissert., Bern, 1888.
Wormser, E. : Die Regeneration der Utenisschleimhaut nach der Geburt, Archiv f.
Gynak., vol. Ixix, 1903 (literature).

VIII.

DETERMINATION OF THE AGE OF HUMAN

EMBRYOS AND FETUSES.

By franklin P. MALL of Bai/hmore.

It would be relatively easy to determine the age of human
embryos were it possible to fix with certainty the time of concep-
tion, that is, the time at which the spermatozoon enters the ovimi.
However, this question, which is directly associated with that of
the duration of pregnancy, and must be discussed with it, has been
a most important one in anatomy for ages, and it appears to be
gradually approaching a satisfactory solution.

In ancient times it was generally believed that the duration of
pregnancy in man, unlike that in lower animals, was of very
uncertain length ; and it was not until the seventeenth century that
it was more accurately fixed, by Fidele of Palermo, at forty weeks,
counting from the last menstrual period. In the next century
Haller found that if pregnancy is reckoned from the time of a
fruitful copulation it is usually thirty-nine weeks, and rarely forty
weeks in duration. In general these results are fully confirmed by
the thousands of careful data collected during the nineteenth
century.

The difficulties encountered in determining the age of an
embryo are due to the impossibility of determining the exact time
of fertilization, for this does not necessarily follow immediately
after copulation, and it is related only in a loose way with men-
struation, the error in calculation in the second case often being
a full month ; but to the present time it has been most convenient,
and probably most nearly correct, to rate the age of an embryo
and the duration of pregnancy from the last menstrual period.
However, from thousands of records it is found that the mean
duration of pregnancy varies in first and second pregnancies, is
more protracted in healthy women, in married women, in winter,
and in the upper classes. As in lower animals, it varies very much
in individual cases independently of any assignable cause. In
general, it is longer when the new-bom infants are over 50 cm.
long, the mean difference being, according to Issmer, fifteen days
between those that are 48 cm. and those that are 53 cm. long.
Furthermore, it is well known that other mammalian embryos
of the same age vary much in size, and, although we have
a variety of data which bear upon the time of conception and

180

AGE OF EMBRYOS AND FETUSES. 181

the age of young human embryos, none are of more value, as Von
Baer has pointed out, than those obtained from comparative
embryology. The first step toward the solution of the problem
was made by Von Baer when he discovered the human ovum.
Next it was proved by Bischoff that ova are usually liberated
periodically during the menstrual period, independently of copula-
tion, and that the Graafian follicles of the ovary which contained
these are converted into corpora lutea. Thus the first step was
taken, for it had been shown that a recent ovulation is marked by
a fresh corpus luteum and that in turn this usually takes place
during the menstrual period.

The excellent work of Bischoff on fertilization in the rabbit
and dog demonstrated that soon after copulation the spermatozoa
pass through the uterus into the tube, where the ovum is usually
met. When copulation takes place during the period of rut the
OAnma is usually fertilized within twenty-four hours, and in case
the ovum is not fertilized upon the surface of the ovary or in the
upper end of the tube it soon degenerates. However, this second
point is not well established for mammals, but it is known that
unfertilized hen's eggs can not be fertilized in the lower part of
the oviduct. Since segmentation takes place in the mammalian
ovum while it is in the uterine tube it is highly improbable that a
human ovum could be fertilized after it has reached the uterus,
but instead is probably always fertilized upon the surface of the
ovary or in the upper part of the tube, as the frequency of tubal
pregnancies indicates.

In 1868 Beichert obtained a very small human ovum measur-
ing 5.5 by 3.3 mm. from a woman who commited suicide exactly
two weeks after her menstrual period failed to appear. This ovum
was studied with great care and described at great length by
Eeichert, and has become the classic specimen upon which to
reckon the age of young human ova as well as to fix the time of
fertilization. In one ovary there was found a well-developed
corpus luteum with but very little blood in its centre. Eeichert
then studied the condition of the ovaries during menstruation and
found that in nineteen specimens out of twenty-three the Graafian
follicles had ruptured in the beginning of the period, while in four
they were still unruptured. From these observations he concluded
that, as a rule, ovulation takes place just before menstruation and
that in case the ovum is fertilized menstruation is missed. This
view changed the entire aspect of the question at once. Formerly
it was believed that the ovum came down the tube slowly and was
fertilized some days or weeks later, and now Eeichert was led to
believe that ovulation and fertilization took place but a few days
before menstruation and that the presence of a microscopic fer-
tilized ovum in the upper end of the tube arrested entirely the
menstrual hemorrhage which was about to appear. With great

182 HUMAN EMBRYOLOGY.

force he discussed the whole question and decided that his
specimen must be two weeks and not six weeks old. Already Von
Baer had noted that the human ovum was precocious in its early
development, but Eeichert's conclusion made it much more so.
However, it was easier to believe that Reichert's ovum was two
weeks than six weeks old and there seemed to be no other
possibility.

The theory of Keichert regarding the time of conception was
accepted by His as the most probable, and accordingly he gave
the probable age of embryos up to 35 mm. long. Due to his great
influence the Eeichert theory has been generally accepted and
the most remarkable distortions have been made to fit individual
specimens into it. The best known case is the Peters ovum, a
specimen 1.6 X 0.9 mm. which was obtained thirty days after the
last period, and Peters estimates its age to be three or four days.
According to Weysse a pig's ovum of the same size is from nine
to eleven days old, and according to Bischoff and Bonnet a dog's
ovum 2 mm. in diameter is from twelve to fourteen days old.
Unfortunately Peters does not describe the condition of the corpus
luleum in this specimen, at present the only reliable index by
which we can hope to determine the age of young ova. It is
imperative that we standardize the corpus luteum of the first weeks
of pregnancy and that in all cases when embryos are obtained at
autopsy the ovaries should be carefully described and sections of
the corpus luteum should be made and pictured.

The ovum of Merttens, 3x2 mm., was obtained from a
uterine scraping twenty-one days after the last period. Here
there was no lapsed period, and twenty-one or fewer days does
not seem to me to be an unreasonable age for a human ovum 3 mm.
in diameter. That the Peters ovum was older than four days is
indicated by the morning sickness that preceded the lapsed period,
and, if I am not mistaken, morning sickness is sometimes the first
sign of pregnancy.

Among the records of embryos under 5 mm. long I have been
able to find thirty-six with menstrual history given (Fig. 147).
According to the Eeichert-His theory about twenty-five days would
have to be subtracted from the ages of twenty-seven of them to
make them correspond with the remaining nine. In other words.
His would rate nine of them from the last period and twenty-
seven from the first lapsed period. We are evidently dealing with
two groups of young embryos which correspond with ovulations
of two menstrual periods, but which two is still uncertain. Must
we add twenty-eight days to each of the group of nine or subtract
twenty-eight days from the group of twenty-seven?

The investigations of Bischoff, Dalton, Williams, Eeichert,
Arnold, Leopold, Leopold and Mironoff, and Leopold and Ravano
have shown conclusively that ovulation and menstruation are

AGE OF EMBRYOS AND FETUSES. 183

usually synchronous, but menstruation often occurs without ovula-
tion and sometimes ovulation takes place in the intermenstrual
period. In Leopold and Mironoff's forty- two cases ovulation
occurs thirty times with menstruation, once without, and ten times
there is menstruation without ovulation. The ninety-five selected
cases of Leopold and Ravano show that ovulation and menstru-
ation coincide in fifty-nine and are independent of each other in
the remaining thirty-six cases. In other words, the connection
between ovulation and menstruation is very loose and the two
coincide in only two-thirds of the cases. Furthermore, ovulation
occurs frequently during pregnancy. [Ravano.]

The data of the other investigators give a similar distribu-
tion of ovulations, and there is no marked evidence that ovulation
precedes menstruation, as is required if Reichert's theory is true.
It is to be hoped that this subject will be carefully studied in some
large clinic where many normal ovaries are examined in abdominal
operations. Then the age of corpora lutea could be standardized
and subsequently applied to autopsy and other cases in which
young ova are found in the uterus. In the recent work of Leopold
and Ravano only the estimated age of the corpus luteum is used
to determine the time of ovulation in relation to menstruation.
At the present time their determination of the age of the corpus
luteum is the best which we possess, but I believe that it is pos-
sible to standardize better the corpus luteum of the first week, that
is, those which are formed during menstruation. This must be
studied first, then that of the second week, and so on. Through
this method we can determine with much greater precision the
probable age of a corpus luteum.

At any rate, the separation of young human embryos of the
same size into two groups to correspond with two previous men-
strual periods indicates that pregnancy usually takes place in the
neighborhood of menstrual periods, and facts regarding the dura-
tion of pregnancy bear this out. Leuckart tabulated 110 cases of
births during the first ten months of married life and found that
the maximum number were on the two hundred and seventy-fifth
day, after which they fell off and increased again to a second maxi-
mum on the two hundred and ninetv-third day. He believes that
in those cases which came in the first maximum the ovum was
obtained from an ovulation which preceded marriage and those
that fell in the second maximum belonged to the first menstruation
after marriage. He was able to collect eight cases in which the
menstrual history was given. In four of them, in which marriage
occurred during the third and fourth week after the beginning of
menstruation, the women menstruated once after marriage. In
the remaining four, in which the marriage followed immediately
upon the cessation of menstruation, three did not menstruate again
and one menstruated but once before pregnancy. In the second

184

HUMAN EMBRYOLOGY.

case, where newly-married women do not menstruate at all, we
must assimae that the ovxilation of the last period gave rise to the
pregnancy; that ovulation delivered the oviun into the upper end
of the tube and soon became fertilized. In the first case the
spermatozoa reach the ovary and there await the ovum from the
ovulation which takes place with the first menstruation after mar-
riage. It follows from the above that a fertilization immediately
before menstruation does not cause the period to lapse, which
contradicts the main proposition in the Reichert-His theory. In
fact women quite frequently menstruate more than once after the
beginning of pregnancy, and at present there are no data to show
that a woman who has not copulated since the last menstruation
cannot be pregnant. Some additional light is thrown upon the
question of the time of conception by a study of the duration of
pregnancy as estimated from the last menstrual period as well
as from the time of copulation. According to the more recent
statistics of Issmer the average duration of pregnancy, in 1220
cases, is 280 days when estimated from the first day of the last
menstrual period, and, in '628 cases, 269 days when estimated
from the fruitful copulation. In general these two figures cor-
respond with those of Ahlfeld, Hecker, and Hasler, who also
collected about 500 cases in which the time of fruitful copulation
was given. So in a group of about 1200 cases the duration of
pregnancy is fully ten days longer when reckoned from the last
period than when from the time of copulation. It may be noted
that the data regarding fruitful copulation must be taken with the
greatest reserve, for many of them are from unmarried women
and in but few of them does the fruitful copulation precede the
menstrual period. However, it is remarkable that the results of
the different observers are practically the same, each time giving
a difference of a week or ten days. Ahlfeld further classified
the cases, giving the time of copulation in relation to menstruation.

Married women . . .
Unmarried women

On last day
of menstrua tloD.

Percent.
35.55
25.49

First twelve days

after beginning of

menstruation.

Percent.

88.44
70.98

First seven days

after end of

menstruation.

Per cent.

88.88
70.58

Similar figures are given by Issmer.

Time of copulation.

First week of menstrual period . .
Second week of menstrual period
Third week of menstrual period.
Fourth week of menstrual period

Average duration of
pregnancy.

277 days
279 days
287 days
285 adys

AGE OP EMBRYOS AND FETUSES. 185

From these figures it is seen that most pregnancies take place
during the first week after menstruation and that the duration of
pregnancy is longer if copulation takes place towards the end of the
intermenstrual period. And this is explained if we assume that in
the first week, especially the first few days after the cessation of
menstruation, the ovum is in the upper end of the tube awaiting
the sperm and that conception immediately follows copulation.
When the fruitful copulation takes place in the latter two weeks
of the month the opposite is usually the case; the sperm wanders
to the ovary and there awaits the ovum; and, therefore, on an
average, pregnancy is prolonged in this group of cases, when de-
termined from the time of copulation. This explanation fits all
the facts but opposes the Eeichert-His theory.

We have finally the argument given by comparative embryol-
ogy. Why should the human ovum be precocious in its early
growth? We have good data upon the rabbit, dog, pig, and sheep ;
and, in general, if we apply the Keichert-His theory, the growth of
the human ovum is at first far more rapid than any of them, and
is then overtaken by the rabbit when 'the embryo is 5 mm. long,
by the pig at 15 mm., and by the dog at 20 mm. The duration of
pregnancy in the rabbit is 30 days ; in the dog, 63 ; in the pig, 120 ;
in the sheep, 154; — ^why should these animals grow slower at first
than man? If the age of human embryos is estimated from the
last menstrual period or a few days later, a curve of growth is
obtained which corresponds fairly well with that of lower animals.

Possibly it may be allowable to compare early human develop-
ment with that of the dog. According to Marshall ovulation in
the bitch occurs after bleeding from the external opening has been
going on for some days, or when it is almost or quite over. It takes
place quite independently of coition. Up to this time the bitch will
not copulate and unless the act is repeated fertilization does not
always take place. Usually the ova are fertilized in the upper end
of the tube, and segmentation is practically completed before they
enter the uterus.

According to Bischoff the growth of the dog's ovum is as
follows :

Diameter of ovum in mm. 0.15 0.14 0.14 0.16 0.16 0.18 0.20 0.21
Age in days 1 2 3 4 5 6 7 8

Diameter of ovum in mm. 0.28 0.30 1.0 2.0 3.0 4.0 5.0 5.0 6.0
Age in days 9 10 11 12 13 14 15 16 16i

Twelve days after copulation are required before the ovum is
as large as Peters 's and thirteen days before it is as large as Mert-
tens's. When it is recg^lled that Merttens's ovum was scraped out
of the uterus twenty-one days after the beginning of the last
period we are inclined to believe that sixteen to twenty-one days

186

HUIVIAN EMBEYOLOGY.

represents its true age. Peters 's ovum, on the other hand, must
be over ^Hhree or four days old"; fifteen is much more nearly its
correct age.

In determining the age of human embryos it is probably more
nearly correct to count from the end of the last period, for all evi-
dence points to that time as the most probable at which pregnancy
takes place. The group of cases from which His did not subtract
twenty-eight days in forming his curve (for instance, Hensen's
embryo, which is 4.5 mm. long and was aborted on the twenty-first
day) are probably much older than His thought. They belong
to those cases in which women menstruated once after becoming
pregnant.

Having determined the time at which pregnancy probably
occurs, it is necessary to fix that at which it ends. Not only is it
necessary to determine the day but also the probable size of the
child, for there is as much variation in the size as in its age.
Issmer gives the following figures:

Size of child

No. of cases.

Age in days, from the beginning of the last

in cm.

menstrual period.

48

203

271

49

272

278

60

252

277

51

211

282

62

123

283

63

34

286

54

18

290

The mean length of the child at birth is 49.5 cm. Hecker found
it to be 51.2 cm. in 985 cases, and Ahlfeld a little over 50 cm. If a
week is allowed to elapse between the beginning of menstruation
and conception then the mean new-born child is 271 days old and
is 50 cm. long.

Having fixed the probable relation between ovulation and men-
struation it is next necessary to relate each embryo and fetus first
to the first day of the last menstrual period and then correct the
same to correspond with the probable time of conception. In order
to do this it is necessary to establish some standard measurements
of the embryo and, if possible, to determine their deviations when
expressed in time.

It is known that embryos of other mammals of the same age
vary considerably in size unless they are from the same litter,
when they are usually very much alike. Undoubtedly there are
variations in different animals, and this must be taken into account
in comparing human embryos with one another. Also we must
not forget that in early abortions there are many pathological
specimens, and even if the embryo is normal in appearance patho-

AGE OP EMBRYOS AND FETUSES. 187

logical conditions are usually the cause of the abortion. This being
true the menstrual periods are also far from normal, and it is
not unlikely that ovulation is more irregular than normal in these
cases. Thus it is often difficult to determine accurately the last
period, for it may be complicated by more or less continuous hemor-
rhage. With all these uncertain factors before us it is certainly
remarkable that the specimens can be arranged as well as they are,
especially their falling into two sharply defined groups during
the first two months of pregnancy.

Until quite recently no serious attempt has been made to de-
termine the age of embryos; it was usually estimated. In order
to do this with some precision Arnold measured embryos from
head to breech and Toldt from the crown to the soles of the feet
(His, 1904). Although this second measurement is called an un-
certain one I think that my measurements show that it varies no
more than Arnold's (Figs. 145 and 146). These two measure-
ments I consider the best that have been proposed. The first —
the crown-rump, vertex-breech, or sitting height — and the second —
the vertex-heel, crown-heel, or standing height — ^are standard ones
used by anthropologists in measuring the body after birth. In
addition to these. His has introduced a measurement for very
young embryos from the elevation on top of the back of the head
to the breech, the Nackenlinie; but this is of little value in measur-
ing older embryos, and easily leads to confusion. In measuring
my own specimens, as well as all those I have found suitably
pictured in the literature, my attention was called to the neck-
breech measurement and its meaning. As it is usually taken it is
of value from the time the embryo is well curled upon itself until
the neck is fairly well developed, that is, from the fourth to the
seventh week. During this period this measurement is the longest,
or is as long as any other, that can be made upon the embryo with-
out stretching the legs. In later stages it equals practically the
length of the vertebral column.

In order to make satisfactory measurements upon the bodies
of young embryos it is necessary to measure them from more fixed
points than is usually done. According to the position of the head
the upper end of the longest measurement of an embryo may fall
over any portion of the brain, and from a study of numerous speci-
mens I find that the middle of the mid-brain is usually just below
the highest point of the head; but whenever this is not the case, as
it is found to be in young embryos, I think the measurement should
still be taken from a point immediately over the mid-brain, as is
shown in Fig. 141, C. The other point which I suggest as a desir-
able one to measure from lies in the mid-dorsal region just above
the first cervical nerve, as shown in Figs. 141 and 142, which have
the outlines of this nerve drawn in. In Figs. 143 and 144 this point

188

HUMAN EMBRYOLOGY.

is marked by passing a straight line from the middle of the lens
through the external auditory meatus to the back of the head. In
both of these specimens this line passes between the atlas and the
occipital bone. This gives an upper point, between the skull and
the vertebral column, which is below the one from which His drew
his Nackenlinie and above the depression in the neck from which
a number of embryologists make their neck-breech measurements.
I have found from numerous measurements of embryos,
fetuses, infants, and adults that a line drawn from the middle of

Fio. 141. — Embryo No. 163, X 10 diameters. C, crown immediately over the mid-brain; R, rump; A^

point between the occipital bone and the first vertebrae; ee, eye-ear line.

the eye through the middle of the ear and extended to the back of
the neck always passes just below the foramen magnum, or slightly
higher. For practical purposes it cuts the skull from the body,
and according to our knowledge of the position of the eye and ear
this should be the case. This line, which I have termed the oculo-
auricular, or eye-ear line, is of fundamental importance in measur-
ing the length of the spinal column in embryos. Anthropologists
obtain the same point between the skull and vertebral column by
extending the plane between the two rows of teeth to the back of
the head; "while art anatomists determine it by projecting a hori-
zontal line through the nasal spine, just below the nares, to the

AGE OP EMBRYOS AND FETUSES.

189

back of the head ; in both cases the skull is cut oflf. All three of
the lines meet in the adult at the foramen magnum; but in the
embryo only the eye-ear line is of practical use, for it can be
determined early and with certainty. The height of the skull,
which forms the submodulus in the Fritsch-Schmidt canon, can be
obtained in any embryo by measuring the distance at right angles
from the above-mentioned horizontal line, through the nasal spine,
to the crown (Figs. 141-144, C), that is, the point immediately over
the mid-brain.

hh^

Fio. 142. — ^Embryo No. 144. X 7 diameters. Letters as in Fig. 141. H, heel; h, hip-joint; K, knee-
joint; X, point in leg which equals the distance from h to i2. By adding xH to CR the standing height of
the embryo is obtained.

The two upper points from which to measure being fixed just
above the atlas and just over the mid-brain, it is necessary to
have a lower point in order to measure the length of the head and
trunk. All embryologists agree that it be placed at the lowest
point of the breech. The line AR approximates the length of the
spinal column and the line CR equals the sitting height of the
embryo. These two lines mark respectively the atlantosacral and
the mesencephalosacral measurements. In Figs. 141 and 142 the
point R is exactly below the sacrum, but as the embryo grows
longer (Figs. 143 and 144) the ischium gradually recedes; at birth

190

HITMAN EMBRYOLOGY.

it is considerably below the level of the sacrum. For practical
purposes, therefore, the line from the foramen magnum to the
rump, AR, equals the length of the spinal column. In the adult
the tip of the sacrum is at the level of the middle of the acetabulum,
and this latter point is naturally chosen by Fritsch in the construc-
tion of his canon. On account of the high position of the ilium in
both the embryo and the fetus, and on account of the close relation
between the lower end of the sacrum and the rump in them, I
believe it most desirable to measure to the rump and not to the

Fio. 143.— Embryo No. 22, X 6 diameters.

acetabulum. Furthermore, it makes one of the measurements,
AR, equal the length of the spinal column, and the other, CR, the
sitting height of the embryo.

A comparison of these two lines upon all four figures shows
that in all cases they are the longest lines that can be drawn from
the mid-brain and atlas to the rump in each case. Furthermore,
as the embryos increase in size the angles these form at the rump
become more and more acute. In Fig. 141 the crown-rump line
falls far in front of the eye ; in Fig. 142 it is just in front, and in
Fig. 143 just behind the eye ; in Fig. 144 it nearly strikes the ear.

AGE OF EMBRYOS AND FETUSES.

191

The entire length of the body, the mesencephalocalcanean line,
or the standing height of the embryo, is really the best single
measurement of the embryo, for it is the one usually made by
obstetricians as well as by anthropologists. It has been said
that the standing height of embryos and fetuses is an unsatisfac-
tory measurement on account of its xmcertainty, but my experience
obtained from the measurement of many embryos, Fig. 146, shows
that it is no more variable, probably less so, than either the sitting
height or that of the spinal column. In Fig. 141 the sitting and

Fio. 144. — ^Embryo No. 131, natural sise. Length of "vertebral eolumn," 68 mm., sitting height (crown-
rump or vertex-breeoh length), 90 mm.; standing height (90 + 21+23), 134 mm.

the standing heights still equal each other, for, as is easily seen,
the leg bud cannot be stretched beyond the rump. The other
figures show that by extending the legs the standing height becomes
greater than the sitting. In each of the figures the hip- and knee-
joints and heel are indicated by letters. If a circle is described
around the head of the femur, as has been done in the figures, the
portion of the length of the leg to be added to the sitting height in
order to obtain the standing height is easily ascertained. In Figs.
142 and 143 this amount is only a portion of the leg, while in Fig.
144 it includes most of the thigh and all of the leg. A number of
fresh embryos were measured in this way, the legs were then

192

HUMAN EMBRYOLOGY.

straightened and specimens were again measured from crown to
heel, and it was found that the two measurements agreed exactly.
By this method, then, the standing height of an embryo can be

90MM

20 30 40 50 60 MM

Fio. 145. — Chart giving the standing height {CH), sitting height {CR), and vertebral column {AR)
measuiements of embryos less than 90 nun. long. The abscissas are CR, and the two series of ordinates
are CH and AR measurements. Each dot represents two measurements of an embryo.

determined without stretching a fresh specimen or injuring a
valuable one after it has been hardened.

By making a large number of measurements of the human
body, Pfitzner has demonstrated that the most constant ratio of

AGE OP EMBRYOS AND FETUSES.

193

400

300

500MM.

200

100

200

Fio. 146. — Chart shown in Fig. 145 extended to indude all fetuaes. The lower

X are all from Burtsoher's measuiexnenta.

300MM.

of specimens marked

any is obtained by dividing the breadth of the head by its length.
The mean index for individuals of every year, from birth to old
age, is 83 in males and 82 in females. I gather from the figures of
embryos and fetuses published by Retzius that in all months of

Vol. I.— 13

194 HUMAN EMBRYOLOGY.

uterine life the index is the same as after birth, for in the indi-
vidual cases given it ranges between 80 and 85. Were it possible
to apply these measurements to all fetuses, I think either the length
or the breadth of the head would prove the best standard, and all
other measurements could be adjusted to it as the art anatomist
has adjusted all proportions to the submodulus. That other
measurements are required of the body of the embryo than those
that are usually made, including that of the entire length of the
body, is indicated by various writers, including His, who was the
first to use the Nackenlinie. More recently he employed a new
measurement which he calls Kopftiefe, and which he says corre-
sponds about to the height of the head, measured from the chin to
the crown. The Kopfldnge is the length of the head, a measurement
which can easily be obtained if this part of the embryo is not dis-
torted. The point between the occipital bone and atlas having been
determined, as is done by the eye-ear line, a second line may be
introduced connecting the spine of the nose with it. The longest
line within the head of the embryo parallel with this measures the
length of the head, and a line at right angles to it extending to the
crown measures the height of the head. Thus it is seen that it is
possible to make some of the ordinary head measurements of the
adult upon the head of the embryo. It may be that the submodulus
of Fritsch-Schmidt may yet prove to be the standard measurement
in human embryology, comparing all of the other measurements of
the body with it, as is the case in the Fritsch-Schmidt canon of the
adult. However, thispossibility appears to be remote.

It seems to me that for the present we must continue to employ
the sitting height or the crown-rump measurement as the standard*
Next in importance is the standing height, and, judging by the
form of a curve made by abscissas and ordinates to determine the
means by the graphic method, I do not find that one is more vari-
able than the other (Figs. 145 and 146). The sitting height is the
measurement most easily, and, therefore, the one usually made
upon young specimens, and the standing height upon older ones.
These two measurements can be compared directly with the two
standard measurements made after birth. By means of the eye-
ear line the point between the head and neck can be marked and
from it the length of the head, and of the skull, may be obtained.
That the standing height is just as good a measurement as the sit-
ting height is further found by the experience of Pfitzner, who was
at first opposed to it, but after having made many more measure-
ments he selected it as the best standard measurement with which
to compare all others. This last statement is based upon the
careful measurements of 5000 cadavers.

All the measurements that I have been able to collect from the
literature, by correspondence, and from my own specimens, are

AGE OF EMBRYOS AND FETUSES. 195

given in the two curves (Figs. 145 and 146).^ These were tabulated
with the crown-rump measurements as abscissas and the standing
heights as ordinates. In the embryos and smaller fetuses a second
set of ordinates gives the length of the vertebral column, and it is
seen that the deviations here are quite marked. The rows of dots
were then divided by curves which included half of the cases, leaving
one-quarter on one side and the other quarter on the other. The
dots which fell between the two lines mark probable deviations and
a line drawn midway between them gives the probable mean. By
this method a probable mean is determined in a graphic way from
a relatively small number of cases. From the two curves the
means of all the measurements in any specimen may be obtained
at a glance. This is necessary, for the age of embryos with the
standing height given had to be compared with those in which the
sitting height is given. In the embryos with a CR measurement
less than 13 mm. long there is considerable deviation on account
of the irregularity of these young specimens, their smallness, and
the great probable error in making the CR and AR measurements.
In embryos 13 mm. long the legs begin to grow and the CR and
CH measurements form a very even curve, but the deviation of the
AR measurement is very marked, showing that it is not altogether
satisfactory.

Having remeasured in three directions after a uniform plan all
the embryos I could collect it is now possible to tabulate them in
relation to the menstrual history, and the curve is by no means as
satisfactory as I had hoped it to be. However, it must stand for
the present, and new and much better material is needed before it
can be revised. Even if we should limit ourselves to specimens
got from mechanical abortions, operations, and autopsies we must
still reckon on 6 per cent, of abnormalities, which are present in all
pregnancies. The cases given in the two curves have been shifted
and tested, and again and again controlled by the curves of Hecker,
Ahlfeld, Toldt, His, Issmer, and Michaelis, and it seems to me that
they are the best that can be done with the data at hand. Towards
the end of pregnancy I have allowed Ahlfeld 's and Issmer *s data
to influence my curve a little ; for a number of the measurements
of my older fetuses came from negroes, and their statements are

*From the literature: Re4zius, MJerkel, Burtscher, Sommerring, Ecker^
Kolliker, 0. Schultze, Kollmann, Heisler, Minot, His, Frederic, Fraser, Keibel,.
Bade, Bonnet, Piersol, Rabl, Tandler, Merttens, Reichert, Peters, Graf Spee, Frassi,
fetemod, Thomson, Hensen, Janosik, Meyer, Stubenrauch, and Wagner.

Through correspondence : From Professors Graf Spee, Laguesse, Hasse, Robin-
son, Edwards, Hrdlicka, Streeter, Jackson, Bruner, Lee, Meyer, Waldeyer, Brachet,
Keibel, Gage, Thomson, Austrian and Mandelbaum.

Together there are over 1000 measurements, of which over 500 have data
relating to the age. Fully half of both these are from my own collection.

196

HUMAN EMBRYOLOGY.

not as reliable as they might be. At the beginning of the curve
I have deviated considerably from His for reasons given above.
Toldt's curve is largely an opinion, as he states in his article.
The other specimens from the latter months of pregnancy (Issmer,
Ahlfeld, and Michaelis) are from exact data and are very reliable.
In transferring Michaelis 's means I placed it in the middle of
the month and not at the end. The His curve is constructed
from measurements taken from his ^ ' Normentaf el, " and the higher
line gives his Nackenlinie. In all other cases the CH measurement
is given as soon as the legs begin to develop.

The great amount of scattering of early specimens, as shown
in Fig 147, is due no doubt in part to an arrest of development,
on the one hand, and continued menstruation after pregnancy, on
the other. In order to get any kind of agreement His, in the con-
struction of his curve of growth, deducted about twenty-eight days
from the age of many specimens in order to make them agree with
the rest. However, his curve which I have introduced is an irregu-
lar one, unlike the probable curve obtained by tabulating any
growing organic body.

Days between

the beginning

Only possible time of

Length of embryo

of the last

copulation between the last

Author.

in mm.

menstruation

menstruation and the

and the

abortion.

abortion.

Embryo anlage, 0.15

38

Exactly 16 dnys

Bryce-Teacher's monograph,
1908.

Ovum, 6.6X3.3

42

20 days before and earlier

Reichert.

Embryo anlage, 1.3 .

34

Exactly 21 days

fetemod : Anat. Anz., vol.
XV, 1899.

Embryo, 3.2

48

40 days before and later

His : A. M. E. II.

Embryo, 6

60

38 days before and later

39 and 41 days before
45 days and later

Kollmann's Atlas.

Embryo. 7

49
57

No. 208.

Embryo, 7}

His.

Embryo, 8.8

42

Exactly 38 days

Tandler : Anat. Anz., vol.
xxxi, 1907.

Embryo, 10

60

49 days and earlier

His.

Embryo, 11

65

31 days (?)

Rabl : Entwickl. d. Gesch.

Embryo, 13.6

63

53 days and later

His.

Embryo, 14

65

Exactly 47 days

Rabl.

Embryo, 30

75

Exactly 56 days

No. 26.

There are a few cases in which the time of copnlation as well
as that of menstruation is given in the history of young embryos.
These I have brought together in the above table, and I have
also entered them with a * in Fig. 147. That is, the age of the
embryo, as rated by the only copulation between the menstruation
and the abortion, is also given. From this it is evident that the
most probable time of conception is during the first week after the
menstrual period, as advocated by Hensen and most obstetricians.

AGE OP EMBRYOS AND FETUSES.

197

HB-

198 HITMAN EMBRYOLOGY.

This view is supported by all the evidence, including that obtained
by the study of early human embryos.

Among civilized races copulation does not take place during
the menstrual period, and it is believed that it is most likely to be
followed by pregnancy if it occurs immediately after the period.
Furthermore, competent authorities recommend that women who
are anxious to become pregnant should copulate before the period
is fully over. If it is true that ovulation takes place towards the
end of the period the ovum is most likely to become fertilized if it
is met by a host of spermatozoa in the tube. After the sper-
matozoa have passed through the tube the probability of fertiliza-
tion is reduced. In such cases pregnancy should occur within
twenty- four hours after copulation. If the sperm awaits the ovum,
as is the case when the copulation takes place some time before the
period, the probability of fertilization is greatly reduced, and if it
occurs it is only after the lapse of a number of days. This accounts
for the discrepancies given by Issmer. That conditions regarding
the relation of fertilization to menstruation and to the oestrous cycle
are identical is further proved by the habit of American negroes,
who, I am informed by Professor Williams, prefer to copulate dur-
ing the menstrual period. At this time the odors of the negress
are said to excite the passion of the negro and are very attractive
to him.

The following table gives the probable deviation of the length
of embryos and of the menstrual age, that is, the age as computed
from the first day of menstruation. I have also included in it the
figures given by Michaelis. Since he gives the mean for each
month I have given his data for the last day of the second week,
for, as I take it, his mean measurements apply to the middle of
the month. The probable age which is the basis for this table is
given in the form of a curve in Fig. 148. It may be noted that
its form during the first month (Fig. 147) is somewhat drawn out
and does not correspond any too well with the curve during the
remaining nine months of pregnancy. However, in embryos up to
10 mm. long the CR measurement is less than that of the spinal
column, while later on it exceeds it. In fact it is the diameter of
a circle in very young embryos, while later on it is half of the
circumference. This Toldt attempted to correct. The His curve
is very irregular in form and for this reason, if for no other, cannot
be correct. It falls between Toldt 's and mine.

AOE OF EMBRYOS AND FETUSES.

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i

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X

X

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2

14

8

21

SI

42

19

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4.5

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26

37

49

25

2.6

10.0

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23

6

35

43

65

32

5Ji

16.0

0

5.6

6

42

51

62

40

11

26

4

11

7

49

59

70

48

19

37

9

17

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56

65

76

56

30

50

16

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63

72

84

61

41

66

32

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70

79

91

68

57

86

33

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77

86

98

76

76

105

45

63

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a4

94

105

83

98

135

68

68

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91

100

111

117

156

SO

81

14

98

108

119

96

146

178

113

149

185

105

100

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105

114

125

103

161

190

130

111

16

112

121

133

109

160

210

166

121

17

119

128

140

117

198

230

172

134

is; 128

1

136

146

125

215

243

187

223

293

196

145

16 133

14S

154

132

2S3

265

207

167

20

140

150

162

137

250

283

227

167

21

147

157

171

144

268

305

246

180

22

154

165

179

161

286

320

256

295

316

245

192

23

161

171

186

156

302

323

270

202

24

168

177

192

162

315

345

282

210

25

176

185 201

170

331

362

300

220

26

182

192 207

176

345

380

315

331

370

308

230

27

1B9

199 214

183

358

400

327

237

2S

196

205,221

189

371

413

340

246

29

203

212 229

195

384

430

355

252

30

210

219

239

200

400

447

370

397

453

363

266

31

217

228

250

206

415

473

276

32

224

234

259

210

426

485

284

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231

241

267

215

436

500

403

293

34

238

248

279

219

448

413

443

477

385

301

ai

246

256

224

460

421

310

36

252

262 296 228,

470

430

416

37

259

271 308

234

484

440

325

S8

266

276 ■ 315

237

494

445

332

3«)| 270

280 320

240

5O0

450

336

■ " Probable deviation " Includes Tulf of the meuuTemenl
t The data of Mlchsellfl are placed In Ibe middle ol tbe m
1 Includes 140 BperimphB.
i figures In biacketa are estlmaUotia

200

HUMAN EMBRYOLOGY.

500 MM»

10 months

Fio. 148. — Curves shown in Fig. 147 extended throughout the ten months of pregnancy. The indi-
vidual cases are not given. CH, standing height; CR, sitting height; AR, length of spinal column. The
curves with the exception of Toldt's and His's are constructed from actual specimens in which the
menstrual history is given. Toldt's is an estimation based upon the literature. His's u an estimation
based upon the Reiohert-His theory.

AGE OF EMBRYOS AND FETUSES. 201

BIBUOGRAPHY.

Ahlfeld: Monatsschrift fiir Geburtskunde, vol. xxxiv, 1869.

Abnold: Inaug. Diss.^ Wiirzburg, 1887.

Von Baer: De Ovi Mammalium et Hominis Genesi. Epistola, Leipzig, 1827.

Entwicklungsgeschichte der Tiere, 1828.
Bischopf: Beweis der von der Begattung unabhangigen periodischen Reifung und

Losung der Eier der Saugetiere und des Menschen als erste Bedingung ihrer

Fortpflanzung, Giessen, 1844.
Entwicklung des Hundeeies, 1845.
Bonnet: Beitrage zur Embryologie des Hundes, Anat. Hefte, vol. ix, 1897.

Entwicklungsgeschichte der Haussaugetiere, 1891.
Bryce and Teacher: Contributions to the Study of the Early Development and

Imbedding of the Human Ovum, Glasgow, 1908.
Dalton : The Corpus Luteum of Menstruation and Pregnancy, Philadelphia, 1851.
Fritsch: Die Gestalt des Menschen, 1899.
Hasler: Inaug. Diss., Ziirich, 1876.
Hecker: Klinik fiir Geburtskunde, 1861.
Hensen: Hermanns Handbuch der Physiologic, vol. vi, 1881.
His: Anatomic menschlicher Embryonen, Leipzig, 1880.

Die Entwicklung des menschlichen Gehims, Leipzig, 1904.
Issmer: Arch. f. Gynakol., vol. xxxv. (For literature upon the history of the

duration of pregnancy, 1889.)
Keibel: Normentafeln, vol. i, 1897.
Leopold: Arch. f. Gynakol., vol. xxi, 1883.
Leopold and Mirinoff: Arch. f. Gynakol., vol. xlv, 1894.
Leopold and Ravano: Arch. f. Gynakol., vol. Ixxxiii, 1907.
Leuckart : Wagners Handworterbuch der Physiologic, vol. iv, 1853.
Loevenhardt: Arch. f. Gynakol., vol. iii, 1872.
Mall : Johns Hopkins Hospital Reports, vol. ix, 1900 ; also Jour. Morph., vol. xix,

1908. (Both papers give many of the measurements which are used in the

construction of the tables and figures of Chapter VIII.)
On Measuring Human Embryos, Amer. Jour. Anat. (Auat. Record, No. 6),

1907.
Marshall: Phil. Trans. Roy. Soc, 1905.

Merttens: Zeitschrift f. Geburtsh. und G3Tiakol., vol. xxxix, 1894.
Michaelis: Arch. f. Gynakol., vol. Ixxviii, 1906.
MiNOT and Taylor : KiebeFs Normentafeln, vol. v, 1905.
Peters: Einbettung des menschlichen Eies, Leipzig und Wien, 1899.
Pfitzner : Zeitschrift f . Morpholog. und Anthropolog., vols, i and v, 1899 and 1903.
Ravano: Arch. f. Gynakol., vol. Ixxxiii, 1907.
Reichert : Beschreibung einer f riihzeitigen menschlichen Frucht im blasenf ormigen

Bildungszustande, Abb. Kgl. Akad. Wiss., Berlin, 1873.
Retzius: Biol. Untersuch., vol. xi, 1904.

Strassmann: in Von Winkel's Handbuch d. Geburtsh., vol. i, 1903.
Toldt: Prager med. Wochenschrift, 1879.
Weysse : The Blastodermic Vesicle of Sus Scrof a, Proc. Amer. Acad, of Arts and

Science, vol. xxx, 1894.

IX.
THE PATHOLOGY OF THE HUMAN OVUM.

By franklin P. MALL op Baltimore.

A LABGE percentage of human ova that are obtained by em-
bryologists are quite unlike the normal ones and therefore they
need special study. From comparative embryology we have
learned that in normal development the tissues are transparent
and sharply defined, and that the organs of the embryo and its
membranes maintain constant proportions in each stage of de-
velopment. Any marked variations from these constants, which
are as yet not well established, are to be viewed as anomalies, but
if they are accompanied by distinctive tissue change of a patho-
logical nature we view the ovum containing them as diseased or
pathological. When the pathological processes of the ovum are
pronounced the villi are atrophied and irregular; the chorion is
thin and transparent, or thick and hemorrhagic; the embryo is
usually dwarfed in an irregular fashion; the exoccelom is often
filled with an excessive amount of dense reticular magma; and
there is usually hydramnios with a granular deposit in the liquor
amnii. These are the chief changes which are easily seen by a
superficial observation of a pathological ovum, and since all of
the changes are relative their recognition depends absolutely upon
a knowledge of the normal form and relation of the structures
within the ovum.

Seventy-five years ago Granville made a report of forty-five
aborted ova, a few of them having complete histories, in which he
concludes that the chorion is first diseased and that this in turn
results in retarding the growth of the embryo. He also notes that
an inflammatory condition must have been present in the uterus,
for the abortion of pathological ova is usually accompanied with
great pain and excess of bleeding. For the present I shall not
consider the etiology of pathological ova, reserving this question
for the conclusion of the chapter.

It is well known that the larger number of abortions occur
during the second and third months of pregnancy, and according
to Hegar there is one abortion in the early months of pregnancy
for every eight or ten births at term. ''A conservative estimate
indicates that every fifth or sixth pregnancy in private practice
ends in abortion, and that this percentage would be increased con-
siderably were the very early cases taken into account, in which

202

PATHOLOGY OP THE OVUM.

203

there is a profuse loss of blood following the retardation of the
menstrual period for a few weeks'' (Williams). Fully twenty
per cent., then, of all pregnancies end in abortion and but 80 per
cent, continue to full term.

Only a portion of aborted ova contain normal embryos which,
judging by their state of preservation, were alive a short time
before they were expelled. According to His, embryos which are
slightly malformed, that is, young monsters, are occasionally seen,
and their condition shows that they were living at the time of the
abortion. His further states that he observed two specimens of
spina bifida, several of anencephaly, one of ectopia of the liver,
and one of cleft palate in ova that were sent to him in the course
of several years. I have had a similar experience. By far the
largest percentage of the specimens, however, contain embryos to
which His applies the collective term abortive forms, characterized
by a general arrest of development.

His also noted that among the embryos sent him by his col-
leagues 22 per cent, were pathological, while in those sent him by
midwives it rose to 40 per cent. In the first group there had been
some selection in the specimens. My own experience, as well as
that of Giacomini, is similar to that of His, for physicians have a
tendency to send good specimens only, and therefore we are of the
opinion that the correct percentage of pathological ova among
early abortions is considerably higher than indicated by His's
statistics. My own records include 434 specimens (Nos. 1 to 404
in my catalogue) of all ages, among which there are 163 patho-
logical ova and embryos of various ages. Among them there are
151 normal and 138 pathological embryos of the first two months
of pregnancy, that is, in embryos less than 32 mm. long. Tor the
sake of comparison I have arranged my data in chronological series
parallel with those given by His.

Total number of Normal and Pathological Ova of thefird two months.

His's collection from all sources

His's collection, only the specimens obtained from

midwives

My collection, first series (Xos. 1 to 126

My collection, second series (Nos. 127 to 208

My collection, third series (Nos. 209 to 379

My collection, whole number (Nos. 1 to 404)

No. of
normal.

62

19
61
24
52
151

Peroentafre of
pathological.

22

40
32
61
56
48

It may be noted that the percentage of pathological embryos
in my first series is much less than in the subsequent series, a
diflference similar to that found by His in his two series. At
first, before 1898, there was also a tendency for physicians to send

204

HUMAN EMBRYOLOGY.

me the normal specimens, but since then I have repeatedly
urged them to send me all specimens, and during the past ten
years the pathological ova of the first two months of pregnancy
have been about 50 per cent. These data are sufficiently good to
be considered representative for America — especially Baltimore.
It may be, and I think it will probably prove to be, that the per-
centage of pathological embryos will vary markedly in different
communities and in different classes of society, to correspond with
the frequency of uterine troubles as well as with the tendency
towards sterility.

My own statistics show also that there are about twice as many
pathological ova in abortions of the first month as are found in
those of the second month. The statistics arranged in two groups
are as follows :

Number and Percentages of Pathological Ova during the First and Second Months of Pregnancy.

PerceDta^
of path-
olc^cal.

Less than 5i weeks old (0-8 mm.) .

Catalogue numbers, 1-208

Catalogue numbers, 209-404

Catalogue numbers, 1-404

From 5i to 9 weeks old (8-32 mm.).

Catalogue numbers, 1-208

Catalogue numbers, 209-404

Catalogue numbers, 1-404

Totals of the above (0-32 mm.).

Catalogue numbers, 1-208

Catalogue numbers, 209-404 ,

Catalogue numbers, 1-404

Total for all months.
Catalogue numbers, 1-404

Normal.

Path-
ological.

26
18
44

59

48
107

a5

66
151

271

33
45

78

32

28
60

65

73

138

163

56
71
59

35
37
36

43
53

48

38

In the first month the low percentage of pathological ova, in
Nos. 1-208, is due to the fact that no effort was made to collect
them before No. 127. Up to No. 127 the percentage of the patho-
logical is 44, but between Nos. 127 and 404 it has been constantly
above 70. The figures and percentages for the second series (Nos.
209 to 404) are, therefore, representative.

According to Marchand 615 monsters were found among
81,187 births, and these figures with the data I have just given
enable me to give the probable number and percentage of abor-
tions and of monsters found in every 100,000 pregnancies.

Pregnancies.

Number 100,000

Percentage 100

Births.

80,572
80

Nonnal
embryos
aborted.

Pathological

ova

aborted.

Monsters

bom at

term.

616
0.6

PATHOLOGY OP THE OVUM. 205

The above table has been constructed from Williams's statis-
tics regarding the frequency of abortion, from Marchand's on
births and monsters, and from the percentage (38) of pathological
ova and embryos I have found among 434 abortions. This table per-
mits the following statement. Eighty out of 100 pregnancies end
in the birth of normal individuals; seven are aborted as patho-
logical ova containing radical changes within them ; and about one
(0.6) produces a monster at term. The remaining twelve ** normal"
fetuses and embryos are by no means all normal, for we are con-
stantly finding in them, especially the younger specimens, minor
changes which must be viewed as forerunners to real monsters.
Teratology will not be on a satisfactory scientific basis until many
embryos with minor changes have been studied with as much
care as Fischel has recently studied several yoimg embryos with
spina bifida, and until the norm has been established with greater
precision for every stage of development.

The line of demarcation between normal and pathological
embryos is by no means sharply defined ; in all probability a num-
ber of the so-called normal embryos are slightly deformed or
abnormal and we must continue to sharpen our conceptions of the
norm. Even those specimens that are obtained directly from the
uterus in operations or in autopsies are by no means necessarily
normal, for a large percentage of all pregnancies contain patho-
logical ova. The probabilities in favor of monstrous embryos is
even greater in tubal pregnancies ; and we should be most cautious
in declaring embryos obtained from them normal, even if they are
well formed and are transparent and alive when they come into
our hands. In passing judgment upon any given specimen we
must continue to rely upon its comparison with well-known em-
bryos of record, as well as with the structure of other mammalian
embryos. Any deviation from the norm as thus determined should
be viewed with grave suspicion, for it is likely to be pathological
in nature.

His has pointed out that the state of preservation of an
embryo is of much value in determining whether it was alive or
not at the time of abortion. An embryo which is suflSciently trans-
parent, or still translucent enough, so that the blood-vessels and
other structures within can be recognized, was probably alive
shortly before or at the time of abortion. Such an embryo is also
probably normal. When they are hardened in formalin or other
suitable preservatives their external contour is in beautiful even
curves, and their sections show the boundaries of the organs and
the histological details sharply defined. These conditions, how-
ever, only indicate that a specimen is in all probability normal.
There is always the possibility that an embryonic monster with
but slight changes has been aborted early in the pregnancy, and

206 HUMAN EMBRYOLOGY.

as more young embryos are studied we find the percentage of them
is larger than we anticipated.

Poorly preserved specimens, that is, those which show signs
of maceration before they were fixed, are not necessarily patho-
logical ; their condition may be due to post-mortem changes, either
before or after the abortion. In case their death took place within
the uterus a certain number of them may show changes in the
amnion and chorion, but even in these cases we are not necessarily
dealing with abnormal embryos. Abnormal conditions of the
uterus may kill a normal embryo without causing it to become
monstrous or to abort. In fact, it seems to be quite common for
the act of abortion to extend itself over a number of days, and
if such abortions are due to the death of the embryo it is natural
that it should undergo some maceration before it is born.

These views, given almost verbatim from His, are now quite
generally entertained ; but I think it likely that he emphasized too
much the early and complete death of the embryo before the
abortion. At the time he first wrote upon this subject he believed
that the primary cause which produced pathological ova lay in
either the germ or the sperm before fertilization, but in his last
contribution to this subject he expressed himself in favor of the
view that the changes in pathological ova are of a secondary nature
due to external influence. In fact, recent work in experimental
teratology, as well as my own studies of pathological human
embryos, bears out this view. In this chapter hereditary mal-
formations, like Polydactyly and muscle anomalies, are not con-
sidered. Pathological embryos, experimental monsters, and human
monsters at term form a class by themselves, inasmuch as they are
produced from normal ova through causes which lie in their
environment.

Embryos that die suddenly are usually aborted at once, and
if they are not they macerate and disintegrate but do not continue
to grow in an irregular fashion as do pathological embryos. The
latter become rounded, grow into nodules or into cylindrical forms,
but do not die immediately. Judging by the well-preserved state of
the tissues so frequently encountered, especially the epidermis, I am
inclined to the belief that they lived up to the time of the abortion.
However, viewed with the naked eye, the embryo is usually opaque,^
the borders of the internal organs are quite obscure, and no blood-
vessels are seen through the skin. Furthermore, the sharp out-
lines of the branchial arches, head, hands, and feet are often want-
ing; the embryo is not dead, but has grown in an irregular way, just
as do fish, frog, and bird embryos when experimented upon. Not
only are the protruding parts of the embryo atrophic, but the
tissues do not move with sufficient rapidity to bring about the
proper form of the subsequent stage, thus producing all kinds of

PATHOLOGY OP THE OVUM. 207

arrestments of development, for example, spina bifida, anenceph-
aly, and cleft palate. In other words, monsters of all varieties and
of all degrees of intensity are produced in the first months of preg-
nancy. As a rule, the changes in them are so radical that they
lead to their own destruction and they are aborted. According to
the table given above twelve monsters are aborted for each one
that develops to the end of a normal pregnancy.

'iei™ of the embryn
w Ai*o uiown.

There are, however, other characteristics of pathological ova
that are more recognizable to the naked eye than are those of the
embryo. The most apparent of these is the diminished size of the
embryo, first described by His (Fig. 149). In order to make this
statement it is necessary to determine the relative size of the
embryo and chorion in different stages of development. The
figures of His, which are given in the first two columns of the
following table, show that the length of the embryo is about one-
fifth of the diameter of the ovum in younger stages and one-third
in older ones.

Chorion.

Protabie
deviation.

2- 4

4-10
10-15
15-20
20-25

Normal

pHibological
(TT specimens).

»«.»

pTob^le

Eitrem«a.

Probable
deviation.

0.2-4

2.0-23
4.0-23
6.0-33

2S.0-50

0.2- 3.5
3.5-10.0
7.0-16.0
13.0-24.0

0-5
2-17
3-20
2-32

From 25-30

3- 7

208 HUMAN EMBRTOLOQT.

The measurements of the chorion include the villi, which may
add somewhat to the great amount of variation in the different col-
mnns. I think It would have been better if the villi had not been
included, for they are also a variable quantity, especially in path-
ological ova.

In the table I have placed after His's figures my own for
both normal and pathological ova. It will be noticed that my
probable deviations vary considerably more than those of His,
while the extremes do so still more.
In fact the probable deviation is so
great that only in extreme cases is the
ratio of the length of the embryo to
the diameter of the chorion of any
value in determining whether or not
the embryo is pathological. However,
the measurements of the pathological
embryos in general are less than those
of the normal, especially in the larger
ova. In a few instances the embryos

Fia. 110. — Ovum amtainms detomlBil , , , , , i ■ • i i

embw s mm. loos. are larger than the normal, which real-

ly should be interpreted the other way
round, i.e., the chorion is too small for the embryo and is markedly
fibrous, while the embryo is nearly normal. Only in the extreme
cases, therefore, are "embryos 4-5 mm. long found in chorions
4.5-5 cm. in diameter, or embryos 2.5 mm. long in chorions
3.5-4 cm. in diameter " (His).

His also pointed out that pathological ova containing small
monsters usually have marked hydramnios. In normal develop-
ment the amnion hugs the embryo quite closely until the beginning
of the sixth week, when its cavity enlarges more rapidly than
the embryo, and by the beginning of the third month of pregnancy
grows to obliterate the exoccelom. In pathological ova, however,
large dilated amnions are found containing small atrophic em-
bryos. In other words, hydramnios is frequently found, just as is
the case when experimental terata are produced in hens' eggs. AH
of this speaks decidedly against the prevailing amniotic theory
of the cause of monsters, which is dependent upon hypo-
thetical amniotic bands and contraction of the amnion early in
development. In addition to the hydramnios found so frequently
in pathological ova the walls of the chorion are often very thin
and transparent (Fig 150), or thick and hemorrhagic (Fig 151) ;
and the villi, which are unequally and poorly developed, are
scattered over the chorion in an irregular manner (Fig 152).
In such ova the villi are sometimes arranged in small groups
forming islands, between which there are large bare spaces
composed of the main wall of the chorion only (Fig. 155).

PATHOLOGY OP THE OVUM. 209

In normal development the exoccelom is filled with a mass of
delicate fibrils which bind the amnion to the chorion. These fibrils,
which do not seem to be connected with cells, give the fluid of the
exocGBlom a jelly-like consistency and form the main part of the
magma reticule of the older anthers. As the amnion advances and

Fia. 151. — Bectjon □! a hemnn-hacic chorion with the adjaeent yolk sulc. The deformed embryo
na 4X mm. long. The vbUb of the umbilical veeide DonUin many blood-venela which oommunisale
directly with than of the ohorioa.

encroaches upon the coelom the fibrils of the magma gradually
form in a layer which finally rests between the amnion and chorion
after the exoccelom is obliterated. A second group of pathologi-
cal ova in which there is no hydramnios often have their exocoe-
loms stuffed with magma reticule, and Giacomini has shown that
its excessive development always indicates that the ovnm is path-
ological. My own experience fully confirms that of Giacomini.

210 HUMAN EMBRYOLOGY.

All stages of an excessive development of the magma are seen,
from those in which the fibrils are but slightly accentuated to
those in which they form a dense hyaline mass (Figs. 153 and
154). In many respects the fibrils look much like those of flbrin,
hut they do not give Weigert's fibrin reaction. As the magma
grows and becomes more fibrous it also often undergoes a gran-
ular degeneration (Figs. 156 and 157), and pathological magmas
are therefore of two varieties, which 1 have termed reticular
and granular respectively. Nor is the magma always confined
to the exoccelom in pathological ova; it may also penetrate the
amnion and more or less fill its
cavity (Fig. 160). However,
this is rare in the ease of retic-
ular magma, that within the
amnion being nearly always
granular in nature (Fig. 161).
In pathological ova irregular-
ities in development may be
seen. The magma may become
too extensive, the amnion may
grow too rapidly, or in relation
to the growth of the chorion
the embryo's development may
be retarded. The changes are
no doubt due to retarded devel-
opment of some portions of the
ovum rather than to death of
the entire structure.

It was mentioned above that
His gradually became convinced
that pathological embryos were
due to secondary changes in embryos which had been normal, a
view advanced long before by Granville. He came to this con-
clusion on account of his study of the structure of pathological
embryos which showed abnormal changes in successive stages
of development. Were the difficulty germinal in origin these
changes should be successive from the smallest to the largest
pathological embryos, and they should not arise from various
stages of normal embryos (Figs. 162 and 163). The real con-
dition of things pointed towards the environment of the ovum
and not to the germ for the cause of the abnormality. It was
difificult for His to come to this conclusion, because at first he was
of the opinion that ordinary monsters in the narrower sense are
due to primary changes in the germ.

His did not examine the membranes of his specimens micro-
scopically, but he has repeatedly referred to changes in the chorion

PATHOLOGY OF THE OVUM. 211

of pathological ova which are recognizable with the naked eye.
In fact, if special care is not taken in the examination of the
chorion of these specimens, one is often inclined to think they are
normal, and this error has been committed by both Giaeomini and
myself. However, triacomini recognized that in some instances
the chorion is not altogether normal
in structure, which he thought
might be due to secondary changes
after the death of the ovum, either
before or after the abortion. In
my own case I was gradually led
to believe that there were two
classes of pathological ova, one in
which the primary trouble is in the
chorion, and the other in the embryo.
In the first group the embryo is
dwarfed and in the second it is de-
stroyed altogether. This conclusion
was based upon anatomical study,
for in the first group the chorion

is usually pathological and in the second it often appears to be
normal. However, more recent studies, with better material than
I had at first, show an ever-increasing number of pathological
membranes in both groups (Figs. 165-168), and I think that this
classification of pathological ova must be abandoned. It appears
now that the membranes of nearly
all pathological ova are pathological,
and, what is more, the deeidua, syn-
cytium, and chorion are frequently
affected in specimens containing ap-
parently normal embryos. The border-
line specimens can not be considered
satisfactorily at present because they
have not been investigated sufficiently.
My more recent investigation of
this question shows that the chorion is
diseased in 113 out of 132 pathological
««^«ulw";^Jl^" ^d.°« 'm^Tf specimens studied. The nineteen in
■ra«m. rttimw, »ithm -■hich there » which the chorion is said to be normal
kcu agio r . show changes in the deeidua in a few

cases, and the rest are mostly older specimens before formalin was
used. Fifteen of them are ova without embryos, that is, speci-
mens in which the embryonic mass was destroyed at a very
early date. In some of these the chorion and deeidua are undoubt-
edly normal in every respect. A specimen 6 mm. in diameter,
which had been scraped out of the uterus on account of chronic

212 HU4IAN EMBRYOLOGY.

endometritis, was perfectly developed, the decidua, syncytium,
and villi being normal ; but it contained no embryo and the ccelom.
was filled with magma reticule and strands of mesoderm cells from
the chorion (Fig. 1G9). But to this case there is a history of
uterine trouble which may have been of sufficient importance to
affect the embryo at a very early stage in its development. Com-
parative experimental ter-
.atology supports this view.
The distribution of
the specimens into normal
and pathological chorions
is given on page 224 with
the table on the distribu-
tion of the embryos. It
shows that in all but a few
cases in which the embryo
was present the membranes
were also pathological.
Fio. i5s.-piioto«™i^of «novumoiMX30x30iiuii., Tlie ohaDges lu the

chorion may now be briefly
given. The most common of all is a fibrous degeneration. The
mesoderm, instead of being beautifully transparent and of even
structure, becomes coarse and fibrous, with the nuclei closely
packed together. There may be atrophy or hypertrophy of the
villi, as well as of the main wall of the chorion. Next we have
(edematous, mucoid and hyaline changes in the villi, in which there
is a tendency to destroy
their structure; in these
there are also often vac-
uoles and larger spaces
containing granules.
These changes may be
found in villi side by side
with others that are nor-
mal, showing that the chor-
ion may have both destruc-
tive and constructive
changes going on in it at

XI. i.- T * * Fio. 156.— ■■8h»do»"of >n ™bryo3Smiii. long lyin«

the same time. in tact within the magma of Uiecnumihown in tli ise

this must also be the case

in normal development, but until the norm of the growing chorion
is established very little can be said about this process. In the
present state of our knowledge pathological changes in the chorion
must be very marked in order to be recognizable.

In many pathological ova the blood-vessels of the chorion
undergo degeneration long before the embryo becomes necrotic, as

PATHOLOGY OF THE OVUM. 213

may be seen from the discussion of this question in my large
monograph. Or blood-vessels may be present after the embryo
is destroyed entirely. At first I was in-
clined to think that in this latter instance
it was necessary to assume the presence
at one time of an embryo nearly 2 mm.
long, for at this time the vessels grow
from the embryo to the chorion in normal
development. Recently I have observed
the growth of blood-vessels, in several
specimens, passing directly from the yolk
sack to the chorion, which proves that it
is unnecessary for the body of the embryo
to develop in these cases (Fig. 170).

The chorion also shows all kinds of
changes of its syncytium. It is often de- v.uu,pu. m..Bm>...i..ecu^.»u.
ficient, irregular, or necrotic, or intermixed

with leucocytes, which may form small abscesses in it. In some
instances, which are not rare, both syncytial cells and leucocytes
invade the mesoderm of the chorion, and thereby hasten its de-

Fio. ISe.— SeclioQ of tbe villui of the ovum shown ia fig. 1ST. S., syncytium.

stniction. The changes in the decidua are harder to follow, because
it rarely remains attached to the chorion and is usually lost.
However, in some instances it was found infiltrated with leuco-
cytes, often in large groups, when the rest of the chorion appears

214 HUMAN EMBRYOLOGY.

to be normal. Above all, this structure is in need of much more
careful study than it has received before the chain of evidence
of pathological ova is complete. However, one point is certain,
disease of the chorion is as com-
mon as are pathological embrj'os,
and the two usually coincide.

In nearly all of the patho-
logical ova a peculiar stringy
substance dotted with numerous
very fine granules is seen between
the villi (Fig. 171). This fibrin-
ous or mucoid mass extends be-
tween the villi after covering
their tips. Within it numerous
leucocytes are frequently seen
(Fig. 174), and into it nests of syn-
cytium often grow. However, the
latter do not radiate and spread

Fio. 160.— Ovum oiDtuning a "aomuil em- aS they do iu UOrmal gTOWth, but

ittimu within [he amniQii. instcad they form clumps or

rounded ends at the tips of long
strands of cells. It appears as if they fail to receive their proper
nutrition from this substance, which is no doubt pathological in its
origin. The constancy of mucoid substance in pathological ova
and the general relations of the tissues which come in contact

Fia. lei. — Ovum 60 rom. in diameter with the embryo incniBled in jranular magma.

with it makes of it a valuable sign of the pathological state. It
is of especial value for this purpose, as it is present in the earliest
pathological specimens before any other marked changes have
taken place in tlie walls of the chorion (Figs. 175 and 176).

Pathological embrj^os were first classified by Panum in his

PATHOLOGY OP THE OVUM. 215

experimental study of early monsters in the hen's egg. This
classification is used as a basis by His for pathological human

in, Luai la, iiic ouapc ui lut; ^ciiu-

inal area is not markedly changed;
") flattened forms with the pro- """'*'■
duction of red blood, that is, the embryo only is affected ; (3) cylin-
drical forms, the embryo becoming abnormal later in its develop-

ment; and (4) amorphous forms. The forms brought together
by Panum under the first group (I) correspond in many respects

216 HUilAN EMBRYOLOGY.

to those described by His in his classification. Among them His
found three main groups of pathological embryos: (1) nodular
forms, in which the embryo is largely destroyed leaving but a small
mass of tissue; (2) atrophic forms, in which the embryo is more
or less distorted; and (3) cylindrical forms, older embryos than

those classed under (•2),in which the head has usually suffered most
by the pathological process. It is easy to see the similarity be-
tween the cylindrical forms of Panum and His in chicks and in
human embryos; in both it appears as if the pathological process
began quite late in development. Amorphous forms can be com-
pared with the nodular forms of His ; in both cases the pathological
process began quite early in development and produced radical
changes in the body of the embryo. His's atrophic, abortive, or

PATHOLOGY OF THE OVUM.

Fio. 166. — S«ctioD of B villua from an oTum of 100X50X40 mm., oonUliiiiig ui embryo 6
long, v., villi; N., oeomlio villug siid ayncytium: H., hyaline desenention □( the memden
■yDcytium: X.. pMuliu- maian of eelli in the meeoderm, probably de^uerated blood-veaHli.

onrly normal and contain b1

218 HUMAN EMBRYOLOGY.

degenerative forms are composed generally of small embryos,
younger than the cylindrical forms and older than the nodular
forms.

His did not recognize a class in which the embryo is destroyed
entirely {Panum's class II, 2), for he had never seen a human
ovum without an embryo. However, such specimens are not rare ;
Giacomini has described a number of them, and I have found many

Fia. IGS,— Section of a villus tram an ovum of 35 X 2G X 15 nun.

more. So in Giacomini 's classification there are two main groups :
(I) those in which the embryo is missing, and (II) those in which
the embryo is present, but deformed. Under tlie second group he
recognizes His's nodular and atrophic forms. In the first group
he classes the ova according to the presence or the absence of
an amnion, and he also gives a third group which presupposes
that the embryo has the power to wander and migrates through
the cavities of the ovum or out of it entirely. I consider this
group unnecessary and fantastic; it includes ova in which the
embryo has been displaced by mechanical means.

PATHOLOGY OP THE OVUM.

^

Fio. I aB, — Section of ths chorion vith alruida of mesenchyme »1Ib i
mm. in diunetcr. M.. Heeenohyme odl>: CA., mil of tbe chorioD; £.. nei
the remnmnt of (he embryo.

220 HUMAN EMBRYOLOGY.

Lastly, I give my own classification in the form of a table in
which the data are arranged with those of His, giving the number
and percentage of specimens under each heading. It is noticed

Fia. 171.— Section of llie chorionio nail o( bq ovum ot 16 X 7 >< 6mm. D.. decidus; 8„ ayDoytiuini V.,

that the percentage is nearly the same in each collection when the
figures are arranged in parallel columns. I always considered it
remarkable that His never observed an ovum without an embryo,

Fia. 172.— Photograph ot an embry

for 28 per cent, of my specimens are of that kind. However, many
of them are bloody or fleshy moles, while others are ova which
appeared to be perfectly normal until they had been cut into serial
sections. I have also compared my vesicular forms with His's
nodular forms, for no doubt they are the same in most cases.

PATHOLOGY OF THE OVCM,

H,.

U&ll.

Number.

Per
cenL

Number.

Per

10 1

u

12

63.4

24.3
22.3

29
16

isj

21
28*

Ova with amDion but without embryo

•This Dumber locludei some of my speclmem ol the teTcath week,— i.e., kll embryo* len than 15 mm. long.

His did not cut sections of the nodular forms, and had he
done so he would probably have found them, as I did, often
composed of a single umbilical vesicle without an embryo, which
"Was frequently not attached to the chorion. The large percentage
<12) of vesicular forms in my collection is probably due to the

Most of the bead la destroyed, but the l*m ii

refined method I have employed in examining these specimens,
most of them having been cut into serial sections.

Giacomini notes especially that it is unnecessary to make a
group to include the vesicular or cystic forms of pathological ova,
for they may be scattered under the various headings of his classifi-
cation. Under this Group I include those in which the entire

222 HUMAN EMBRYOLOGY.

embryo has been destroyed, leaving only the umbilical vesicle and
sometimes a portion of the amnion. The remnants of the embryos
of this group correspond well with Panum's II, 2, in which the
embryo is destroyed but the area vasculosa remains and gives
rise to blood, just as the vesicle in this form of human monster is
composed mainly of an umbilical vesicle with its primary blood-
vessels. It may be noted that some of these umbilical vesicles
have been confused with the amnion in Giacomini's fantastic
group, in which the embryo has wandered out. It is further stated
by Giaeomini tliat the openings through which the embryo wan-
dered often healed up, for they could not be found.

Fid. 174.— BaetiOD of tbedsddiu. villi, ud cborion of the specimen sbowD in Fig. 172. There la n mua
of muiwa tMtweeo tb« villi wb^ch wntaini nuny leucooyUe.

In the nest table I have arranged nearly all of my pathological
ova under various headings, omitting only a few embryos over nine
weeks old.

Group I. — In the first group are the vesicular forms in which
the main remnant of the embryonic mass is composed of the
umbilical vesicle (Figs. 176a-178). In some of them the amnion
is formed and in others it is destroyed entirely.

Group II. — In the second group there is neither amnion, em-
brj'o, nor umbilical vesicle; only the chorion remains. This group
must have formed from that variety of Group I in which there is
no amnion present. Vesicular and solid moles may arise from
this group.

PATHOLOGY OP THE OVUM. 223

Group III. — In this group the embryo was destroyed after
the amnion had been formed; usually it lines the chorion. All

Fia. 176. — Seetion through the tipe of the viUi of tn oiTim M mm. Id dtametar. The embryo
in. 2 mm. loag, is delanaed but nearlr iuiiiiibI. S^ Byiuvtium: K., villa*; F., fiacmeuted uuola;

, necrotie synoytium.

tured in Fig. 176.

stages of the complete destruction of the embryo are found in this
group, from a necrotic, granular mass to a vesicular ovum lined
by the amnion with but a very short stump of the umbilical cord
left (Fig. 179).

HUMAN EMBBTOLOGT.

oj the Chorion.

altolheOmdiiion

CR

Nnmber.

Per
cent.

Condltton or the chorion.

Momul.

oJ^,.

rJJSd

1

11

26
32
43

19

29

16
4
18
21
13
27
10
2
1

12
18

10

3
11
13

8
17

6

1.4
£

6

6

3
0
1
0
0
1
2
0
0

11

22

11
3
11
15

10
23

4
2

II. Ova with neither amnion not

III. OvR with amnion but without

IV. Embryos of the 4th week ..'. ...

Embrj-OB of the 5ih week

Embryos of the SJth week

Embryos of the Sth week

Embryos of the 7th week

Embryos of the Sth week

Embryos of the 9th week

Embryos of the 10th week

1

6
S
3
3

4
0
0

169

100.O

19

113

Gboup IV. — The embryo is present in this group and is more
or less degenerated. In case it is much degenerated it may pro-
duce a nodular embryo of His or an amorphous embryo of Panum.
Usually after the fifth week it is quite easy to recognize the stage
in which the embryo became pathological. The younger ones
correspond with His's abortive, atrophic, or degenerated forms.

I, lbs Fio. 177. — Ovum

the older ones often with his cylindrical forms (Figs. 180-183).
I have found it more convenient to arrange them in weeks accord-
ing to the age of the embryo at the time the pathological process
began. The embryos of any given week may contain any of His's
atrophic forms according to the extent, degree, and duration of the
pathological process. It is noteworthy that there are so few path-

PATHOLOGY OP THE OVUM. 225

ological embryos of the fourth week in my collection, while
relatively there are four times as many in His's collection. Just
the opposite is the case with the vesicular or nodular forms. It

Fio. 178.— Section Ibrouifa the vesicle withio the ovum ebown in Fie. ITT. The double vnide
' 3.3 mm. The imoLker vende betwBflQ the larfer one And the chorion may bt the Ainni-
otio (Bvity or poagibly the dil«(«d kllkntoie, althmifh it ia not *tt««hed to the choriaa.

may be that I have had a tendency to class with these embryos
those that he classes with the nodular form. The vesicular forms
are intermediate between ova without embryos and ova with path-
ological embrj'os of the fourth and fifth weeks.

The largest number of pathological embryos are formed dur-
ing the first seven weeks of pregnancy; their number falls off
markedly in the eighth and ninth weeks ; and but very few occur

Vol. I.— 15

HUMAN EMBBTOLOGY.

Iiotograph oik pcthotnckal onbryo 0 Fia. 181. — Section

Fio. 183.— Sd^tUl necti

after the tenth week. Patholo^cal embryos that survive the
second month will probably eontinue throngh the normal period
of pregnancy and give birth to monsters. From statistics given
above, this should be the case in every twelfth pathological ovum.

PATHOLOGY OP THE OVUM. 227

It may also be suggested, with Giacomini, that threatened
abortion in early pregnancy should be encouraged, for the cause
of it is probably a pathological ovum and the uterus should be
relieved of it. Careful investigations should also be made in
these cases regarding the cause of the primary trouble. Sterility,
or tendency towards sterility of women, especially if it is acquired,
should be studied much more carefully than it has been for the
sake of scientific teratology and the scientific treatment of abortion.

The study of pathological ova has shown tiiat the embryos
within are deformed and that there are structural clianges in the
chorion which appear to be associated with inflammatory processes
in the uterus. The villi are usually fibrous or are otherwise de-
generated, the syncytium is atrophic or necrotic, and there is an

Fia. 184.— Embiyo 3S nun. k>n< from a tubal pncunoy.

excess of blood and mucus rich in leucocytes between the villi.
These are also often invaded by syncytial cells and leucocytes.
The picture indicates that the chorion is affected by an inflamed
uterus, which naturally interferes with its nutrition. It is prob-
able, however, that the process is somewhat more complicated, for
the trouble often seems to lie within the decidua, especially in
tubal pregnancies, which nearly always contain pathologcal ova
(Fig. 184). In such cases the inflammatorj-- process around the
chorion is not so marked, but the decidua is deficient and there
is an excessive amount of blood between the villi {Pig. 170). In
both cases the nutrition of the ovum is affected, in the uterus
by inflammatory and in the tube by hemorrhagic processes, which
interfere with its implantation. As a result of faulty implanta-
tion the chorion degenerates or its further growth is retarded
and the embrj'O suffers and becomes atrophic.

On the other hand, it is also possible to view the change in
the chorion as secondary, as a result of primary changes in the
embryo which are germinal in origin. In fact this view of them
is entertained by many pathologists, who would consider the ovum

228 HUMAxN EMBEYOLOGY.

as a foreign body after the death of the embryo, and all of the
inflammatory changes found within it as of a secondary origin, as
would be produced by a sponge if it were put in its place. This
second attitude, which considers the changes within the embryo
and in the chorion as a coincidence, is, I believe, incorrect. To be
sure, it is well known that a woman who aborts a pathological
ovum or gives birth to a monster is more likely to do so again,
and this is the great argument in favor of the theory that the
primary trouble lies in the germ and not in its environment. How-
ever, if pathological ova and monsters are due to a diseased condi-
tion in the uterus which interferes with the implantation of the
ovum, this fact speaks equally as well for the environmental as it
does for the germinal theory. The facts bearing upon these two
theories I shall give briefly and in the order of their value.

1. It is shown in the table given in the beginning of this chap-
ter that of all pregnancies 7 per cent, end in pathological ova. In
case the pathological condition is present in either the germ or
sperm that same percentage of pathological ova should be found in
ectopic pregnancies. I have taken considerable trouble to investi-
gate the evidence obtained from tubal pregnancies, and in general
find stated in the literature that more deformed embryos are
found in them than should be; but this statement is rather an
opinion than a demonstration based upon actual records. The
answer to the question is complicated and rendered difficult by
the rupture of the tube, which is of frequent occurrence, through
which the embryo is easily lost in case it was present. I have col-
lected all the cases of unruptured tubal pregnancies from Dr.
Kelly's gynaecological laboratory- and find that there are forty-six
in which the tube has been examined by refined modem methods.
The enlargement in the tube containing the ovum measured in
these specimens from 1 to 6 cm. in diameter, and in thirty-nine of
them remnants of the chorion were found with villi ramifying
through the blood-clot. Five contained pathological embryos,
and but two contained normal embryos which were of the second
month. In these two the chorion was well implanted, having a
well-formed decidua, as is usually the case in the uterus. In all
the rest the villi were of irregular shape, usually atrophic and
degenerate, sometimes very long and thin with much blood between
them, and the decidua was irregular and scanty. In these the
implantation was faulty, and as a result 96 per cent, instead of
7 per cent, became pathological or produced monsters. This is
the strongest argument against the germinal theory.

2. Von Winckel has done us a great service in collecting the
data regarding the condition of live fetuses which had been re-
moved from ruptured ectopic pregnancies by surgical operations.

PATHOLOGY OF THE OVUM. 229

They, of course, were derived from the 4 per cent, of normal
embryos mentioned above, for the pathological changes in the 96
per cent, were so radical that they could not develop into fetuses
of any kind. Von Winckel's specimens are especially valuable,
inasmuch as they show the possible fate of the normal embryos
I found in tubal pregnancies obtained from Dr. Kelly's clinic.
Forty-seven out of eighty-seven fetuses were much deformed and
twelve were markedly monstrous; but eight were really normal.
Among the monsters there were six specimens of hydrocephalus,
one each of hydromeningocele, spina bifida, encephalocele, anen-
cephalus, omphalocele, and hypospadia. In addition, the head was
deformed fifty-seven times, legs forty-four, and arms thirty-five,
with club-feet in twelve and amniotic bands in four cases. The
placenta was usually deformed, sometimes multiple and sometimes
broad, thin, or short, and often very hemorrhagic. In general,
the poles of the body suffer most, the head being deformed in 75
per cent., legs in 50 per cent., arms in 40 per cent., and the trunk
in 4 per cent, of the cases. It is clear that the difficulty is due
largely to ordinary mechanical causes which interfere with the
growth of the placenta and the poles of the embryo and frequently
produce typical monsters. From the data given, it is seen that but
very few of the embryos in tubal pregnancies produce normal
individuals.

3. Comparative experimental teratology has shown us that
all varieties of monsters found in man can be produced in large
numbers from normal ova after fertilization as well as from
normal embryos. I can only enumerate the results, the literature
and general discussion having been given in my larger mono-
graph, as well as in Hertwig's **Handbuch."

a. Polysomatous monsters can be produced by a variety of
mechanical methods from normal eggs. Thus Vejdowsky showed
in 1892 that the number of monsters produced from Lumbricus
eggs was greater in the summer months than in cool weather ; and
somewhat later Driesch succeeded in producing monsters from
sea-urchin eggs by separating the cells in the two-cell stage by
mechanical means, or by increasing their temperature, which
acted upon them in a similar way. Somewhat later Loeb pro-
duced double monsters from sea-urchin eggs by changing the
chemical composition of their surrounding sea water. In case it
is diluted its rapid absorption by the egg causes the cell mem-
brane to rupture, through which some of the protoplasm often
escapes; upon returning the egg to normal sea water segmenta-
tion begins, nuclei wander out into the extruded protoplasm, and
a double monster develops.

These important discoveries were next extended to verte-
brates by Wilson, who experimented upon AmpMoxxis; and then

230 HUMAN EMBRYOLOGY.

by 0. Schultze, who experimented upon frog eggs. Both terato-
logists used mechanical means to produce double monsters. Wil-
son shook his eggs after segmentation to form hour-glass shaped
eggs, and Schultze fixed the eggs between two glass slides and
inverted them after segmentation had begun. The partly sepa-
rated blastomeres gave the anlagen for the bodies of the two
embryos, and recently Spemann has produced double monsters in
the frog by tying its eggs with a fine thread at the right time.
Furthermore, Tornier has produced double legs or even clusters
of legs from the single anlage of the leg. These experiments all
show that polysomatous monsters are produced from normal eggs.

b. Another variety of monster, not well developed and poly-
somatous, but atrophic and merosomatous, is found in lithium
larvae. In 1893 Herbst found that there was often an inversion
of the blastodermic membranes in case developing sea-urchin
eggs were subjected to the action of lithium salts. Morgan ex-
tended these experiments to frog eggs and found that the inversion
of the layers was due to a failure of the upper protoplasmic
contents of the egg to move downward, and he concludes that this
arrest is due to the physical and chemical action of the lithium.
These monsters are similar in appearance to the irregular nodular
forms produced by Panum, Dareste, and Fere, and are interesting
inasmuch as they show that the action of lithium upon a normal
egg is specific; the lithium produced a definite action upon the
egg, interfering with its internal growth and also with its nutrition.

c. It has also been shown by Loeb that the action of calcium
salts upon eggs has a specific action upon the growth of the heart
and blood-vessels, by preventing the heart beat and retarding the
growth of the blood-vessels, as well as of the embryo in general.
Although Loeb states expressly that the action of the calcium is
specific, as the rest of the embryo remains normal, I am inclined
to believe him in error regarding this point, because he did not
examine his specimens microscopically and because Knower has
recently shown that mechanical enucleation of the heart in young
embryos is followed by the gravest consequences. In such em-
bryos the pronephros becomes oedematous and the lymph- and
blood-vessels and body cavities become distended. There is a
general arrest of development of the embryo; the coils of the
intestine are atrophic and there is histolysis of the mesentery and
vacuolation of the muscle cells. Teratologists recognized long ago
that the heart must be affected more or less in monsters, on account
of the frequent occurrence of an oedematous condition of the tis-
sues, as well as of accumulation of fluid in the serous cavities and
of the hydramnios and hydrocephalus. Such conditions are often
seen in pathological embryos, as well as in the monstrous chicks
which were produced experimentally by Panum and Dareste.

PATHOLOGY OF THE OVUM. 231

d. In 1892 Hertwig published his remarkable essay on spina
bifida, which is of far-reaching importance. However, it was
Morgan who discovered that spina bifida may be produced experi-
mentally by subjecting frog eggs to the action of common salt.
It was found that a 0.6 per cent, solution delays the development
of the egg (the chorda, intestine, myotomes, and nervous system
developing normally), but gastrulation is postponed for from
twelve to twenty-four hours. Posterior spina bifida naturally
results. Later in development the exposed cord undergoes
cytolysis and histolysis. Subsequently Hertwig extended Mor-
gan's sodiima experiment to axolotl. Here the reaction is sharper
than in the frog and there is also often anencephaly. It was found
that a 0.5 per cent, solution had no effect upon the embryo at all,
a 0.6 per cent, solution made half of them monsters, and in a 0.7
per cent, solution all of them developed spina bifida. Schaper
has removed the brains of tadpoles mechanically* and Harrison
has done the same with the spinal cord. In these experiments
the embryo grows normally without spinal nerves or cord unless
the operation destroys the lymph hearts also ; then dropsy follows.
In fact this seems to be always the case when the heart is involved
by either mechanical or chemical means.

e. The great precision by which spina bifida is produced by
the action of sodium salts is equalled in a more striking manner
by Stockard's magnesium experiments, in which typical cyclopia
is produced in 50 per cent, of the fishes {Fundidus) experimented
upon. Teratologists have speculated upon the cause and the de-
velopment of cyclopia for centuries, and now with one stroke all
is clear. Ten years ago Born occasionally produced cyclopia by
splitting the head of the embryo through its sagittal plane. Later
Spemann produced the same by ligature of the head, and Levj'
by cutting off the front tip of the head. Harrison also often pro-
duced a new variety of cyclopia by removing the brain of the
embryo; the eyes then wandered to the back of the head in the
region of the pineal eye and appeared to unite. By a very dif-
ferent method Lewis succeeded in producing cyclopia in a large
percentage of the specimens experimented upon. He pricked the
extreme end of the embryonic shield of Fundulus and from such
eggs embryos with all degrees of typical cyclopia developed. Of
course, the striking experiment is Stockard's, and recently he has
given an account of the anatomy of his embryos. At any rate, all
these experiments show that all kinds of monsters, including spina
bifida and cyclopia, are produced from normal embryos due to
external influences.

4. The consensus of opinion of gynaecologists is that patho-
logical ova are due to a diseased uterus, but they are not inclined,
to associate pathological embryos with monsters. Neither do they

232 HUMAN EMBRYOLOGY.

speak of curing the uterus of women who have given birth to
monsters in order to prevent them from doing so again. How-
ever, the evidence I have given above proves that monsters are
produced from normal eggs by conditions which either interfere
with their nutrition or poison them, and that in tubal pregnancies
there is a great excess of pathological ova and monsters. How
is it with pathological ova which come from the uterus! Is the
uterus usually normal, or pathological! The chorion in nearly
all pathological ova examined shows signs of inflammation, often
severe, which is, of course, uterine in origin. Taking all of the
pathological ova in my collection, thirty- three altogether, in which
any data regarding the women from whom they were obtained
are given, it is found that they are easily arranged in three groups.
(1) In the first group of eleven cases the main trouble preceding
the abortion was a severe hemorrhage extending over a number
of days. (2) The second group of twelve specimens were abor-
tions from first pregnancies in newly married women or relatively
sterile women who had been married for some time and were
anxious to have children. (3) The third group of ten specimens
were from women who had given birth to a number of healthy chil-
dren and then began to abort, often a second or a third time. The
first group throws no light upon the question we are discussing,
but the second is of value because it comes from sterile women.
The third group is more easily explained. The women, perfectly
healthy at first, gave birth to one or more children and then con-
ceived and aborted quite regularly. In these cases the uterus was
normal at first, but later, due to a variety of infections, became
inflamed, and thereafter the fertilized ovum could not implant
itself, became pathological, and was aborted. My records also
state that seven of the women are healthy and twelve have uterine
disease. In general, those with uterine disease belong to the
second and third classes mentioned above. It may be noted that
all the pathological conditions of the ova of the third group could
not be due to germinal causes, for all these women had given birth
to healthy children and the probabilities for any class are but 1 to
14. The data only confirm those obtained from tubal pregnancy,
as well as those from experimental teratology, that is, the primary
cause is in the environment.

5. Especially interesting are those cases in which two path-
ological embryos are obtained from the same woman. Five such
sets are in my collection, and in four of them the changes in those
of a set are alike. Two sets are duplicate twins and one is com-
posed of two twin ova from a woman who had aborted before.
The fourth set are about a year apart from a woman who had had
nine children, after which her health failed (ten years Bgo) ; since
then she has conceived regularly and aborted every time. The

PATHOLOGY OF THE OVUM. 233

chorions of these two specimens are well infiltrated with leuco-
cytes, the villi are largely destroyed, and the changes in the two
embryos are severe and much alike. The fifth specimens are from
a young woman, mother of two children, and the first of these
appeared normal with the exception of an excessive amount of
granular magma in the amnion, with leucocytic infiltration of the
placenta. Nine months later a second typical pathological embryo
was obtained from the same woman. Disease of the uterus began
with the birth of the second child. Later she aborted again.
Although these cases do not prove the point made they at least
indicate that the same environment affected the ova of either
successive or twin pregnancies in the same way.

The theory that merosomatous monsters are produced by
mechanical influences was established by Lemery, defended by the
Saint-Hilaires, but was antagonized to the utmost by Meckel,
Bischoff, and others. In case they are produced from normal
embryos by means of external influences it follows that the embryo
must become wholly or in part diseased or pathological, a view
entertained by Morgagni. Frequently the pathological changes in
the fetus were compared with those in the adult and it was be-
lieved that they were also due to a variety of diseases, such as
syphilis, tuberculosis, rickets, or to inflammation. However, it
was impossible to show that the destruction of tissue necessary to
produce a monster was associated with pathological changes
peculiar to these diseases, but instead they nearly always appeared
to be normal in character. Panum defended the nosological
theory and asserted, with good reason, that only the fundamental
characters of the changes within the embryo in a given disease
should be like those in the adult. In fact he asserted that the
nomenclature for the pathological changes in the embryo cannot
be the same as that for the adult, and this opinion is borne out by
the numerous investigations during the last fifty years. At best,
Panum states, the etiological factors are the same for diseases of
the embryo and of the adult. He had found in experimental chick
monsters due to malnutrition that there are constant tissue
changes, such as will produce exudates, bring about adhesions, and
cause atrophy with scar formation. And since these changes are
found constantly it indicates that they are due to a common path-
ological cause. Local softening and necrosis, which often accom-
pany the above-mentioned processes, are of sufficient importance
to account for the changes in development, which is otherwise
normal, to produce spina bifida and the like. These changes, which
often take place in the embryo before the blood-vessels are formed,
may be likened to those accompanying inflammation in the adult.
However, there is a multiplication of cells as well as a cell necrosis,
and Panum thinks himself justified in calling the process parenchy-
matous inflammation of the embrvo.

234 HUMAN EMBRYOLOGY.

The tissue changes found by Panum in experimental chick
monsters were subsequently seen and recognized by Giacomini,
His, and myself in the human embryo, and are well described by
Giacomini in his general article. By means of serial sections of
pathological embryos it is easily seen that the sharp normal lines
of demarcation of the structures are largely lost in young embryos ;
and in older embryos the elements of different organs become
more or less mixed, which often gives them the appearance of
lymph-glands. However, certain tissues like the ectodermal are
more resistant than others. The changes in older embryos were
described with great accuracy by His. He stated that the blood-
vessels of pathological embryos enlarge and become gorged with

blood, and that many of the cells wander into the surrounding
tissues, thus converting the whole embryo into an even structure,
as described by Giacomini.

It seems to me, in view of what has been said above, as well
as by the results of Born upon grafted embryos, and of Hertwig,
Morgan, and others upon numerous experimental monsters, that
we are dealing with a condition in which there is more or less
correlation of growth, which may represent a fundamental type
of inflammation. When, however, the embryonic tissues become
mixed, which is generally due to malnutrition followed by some
cytolysis, we have a new condition quite unlike any pathological
change found in the adult. The repair of a simple wound in the
embryo is always associated with further development of the sur-
rounding parts, and in case the process ends in a perfect result
normal development still remains, with or without regeneration ;

PATHOLOGY OF THE OVUM. 235

bat If there is a lack of correlation, pathological conditions arise,
already recognized by Morgagni, and well described by Panum,
Giacomini, and His. This pathological condition I shall term
dissociation. The growth of dissociated tissues may be checked
by excesssive cytolysis or they may be de-
stroyed entirely by histolysis.

There are several young embryos in
my collection in which dissociation is just
begimiing. One of them, 2 mm. long,
which is practically normal in form, is
from au ovum which was curetted from
the uterus and included part of the de-
cidua (Fig. 185). The decidua is infil-
trated with leucocytes and the eoelom has
in it an excess of magma reticule; other-
wise the chorion appears normal. The
front end of the amnion is torn and well
packed in with magma, showing that it too
is not of mechanical origin. In general,
this specimen shows that in young path-
ological ova the embryo is extremely susceptible and about the
first to suffer. In this specimen the mesodermal tissue of the
embryo and the ventricles of the fore-brain are filled with round
cells containing fragmented nu-
clei. Most of the blood-corpuscles
are still within the blood-vessels,
and those that are free in the
tissues are well defined and per-
fectly normal in appearance.
However, it may be noted that
the cells of the mesenchyme di-
minish as the free round cells in-
crease, showing that they are dis-
sociating, as are also those of the
brain tube. Another specimen,
somewhat more advanced in de-
velopment, has an atrophic head
and a wide open spinal cord be-
low, anencephaly and spina bifida
(Fig. 186). In this there are
f.r^-Z^r^S'^: ^^,.Tri.^:LtTJtf slight signs of its pathological
the ovum « BO ram. The abortion took pUce 18 nature in the chorion, and there

weeki aller the last menslruttl penod. . . n

IS an excessive amount of magma
in the eoelom. So far there is no dissociation of the tissues of the
embryo; there is only an arrest of development of the central
nervous system. As the pathological process continues in later

236 HUMAN EMBRYOLOGY.

embryos of the fourth week, the amnion is often destroyed and
tlie embryo rapidly degenerates, usually leaving the umbilical
vesicle, which is quite resistant. Subsequently this is also de-
stroyed, leaving only the chorion, without amnion or embryo, which
may continue to grow into an irregular mole.

The embrj'o gradually becomes more and more resistant
during the fifth week, the brain and heart showing somewhat
greater resistance than tie other organs. -Between the fifth and
sixth weeks, when the peripheral nervous system appears, the

delineation of the organs becomes sharper. Here we also often
find dissociation of one or more of the tissues or organs, a gorged
vascular system, and frequent hydrocephalus, all probably due to
an arrest of the heart action. Such embryos rapidly undergo
secondary changes and within a month most of them abort, or if
the chorion remains it may form the nucleus of a mole.

During the sixth week, owing, no doubt, to the unequal dif-
ferentiation of the tissues, some of them become more resistant
than others. The more central tissues stand the action better
and the more peripheral tissues are more susceptible. Thus the
spinal cord and medulla do not dissociate and atrophy so easily

PATHOLOGY OP THE OVUM.

237

as do the head, face, brain, and ex-
tremities. The vascular system also
suffers very much, probably on account
of the effect of the impaired nutrition
of the chorion upon the heart. As a
result of the weakened heart the cavi-
ties of the brain and body become
dropsical, and the tissues of the ex-
treme ends of the embryo dissociate
and develop poorly. The precartilage^
and cartilages suffer least of all.

In the beginning of the seventh
week the cartilages of the extremities
are outlined, and at the end of this
week ossification centres make their ap-
pearance. Coincidently the peripheral
nerves ramify through the body and
the muscle anlagen appear. On account
of the high degree of differentiation of
the structures of the embryo, impair-
ment of its nutrition produces very
imequal effects upon its organs and
tissues. In the earliest stages the
umbilical vesicle is the most resist-
ant, liien the nervous system, and now
it is the skeletal tissues. Before the
development of the heart, the blood-
vessels were verj- resistant; now that

they are dependent upon the heart they
are least resistant, and structures which
are dependent upon the circulation for
their nutrition suffer in a secondary way.
The changes in embryos of the seventh
week can be followed easier than those in
earlier embryos, for they are less rapid
and the differentiation of the structures
aids the observer very' much. Now the
extreme ends of the embryo are pro-
foundly changed (Fig. 187), due probably
to affections of the heart of the embryo;
there is much cytolysis and dissociation
of the nervous system; and the face, head,
and extremities are often atrophic. To-
wards the eighth week there is a great
Fia.iM.— Reomatnictioaoftha diminution of the number of pathological
2* mip. long. Bhowing .pin. bifid*, ova lu mv collection, as was also th6 case
X'^ft?i^!'°^'^"*'"~" in that of His. It follows that most

238

HUMAN EMBRYOLOGY.

monsters are fortned before the eighth week; those with radical
changes in them are aborted, while those that are slightly affected
continue to develop until the end of pregnancy. However, many
of those that are aborted show considerable growth of a variety
of structures, such as the epidermis, which proves conclusively
that we are not dealing with post-mortem changes in the embryo.
The longer such a specimen remains in the uterus the more radical
are the secondary changes in the embryo and the more pronounced
are the primary changes in the chorion. In order that a monster
shall continue throughout pregnancy the changes in the embryo
must not be extreme enough to eliminate the heart, and the chorion
must be normal enough to permit the formation of a healthy
placenta, which begins to differentiate at the time (end of the
second month) monsters cease to form.

In the following table I have arranged the data regarding
the percentage of the varieties of monsters found in pathological
ova, and at birth. In general they agree very well. However,
the percentage of spina bifida is greater in the embryo than at
birth, indicating that the mortality is greatest in this variety of
monster. If the larger number of cases of dropsy of the head were
reduced or omitted, the proportion of monsters in pathological
ova and those at birth would agree very well. No doubt water
on the brain is an affection primarily of later fetal life, but this
question remains to be investigated.

Percentage of Monsters in Pathological Ova and at Birth,

(Panum).

Varietiefi
of monsters.

Anencephalus . . .
Hydrocephalus . .
Hydrocephalooele .

Harelip

Cyclopia

Eyes missing

Defd upper jaw...

Def d extremities. .

Spina bifida

Total

(Von Wisckel).

r Upper extremity
\ Lower extremity

Back

Abdomen

496 i 100

:l).

•

B

a

23

31

12
4

21

9
17

35

3 ' 4

7 9

75

100

(Mall).

79 monsters in 163

■

%

pathological ova from

484 specimens

S

collected.

S5

24

Atrophic head

Malfd face a neck

17

Displaced eyes

3

DePd extremities.

18

Spina bifida

12

Exomphalos

5
79

s

0k4

31

1

25

23

15
6

100

The specific action of salt solution upon amphibian eggs, pro-
ducing a large percentage of spina bifida monsters, has been
mentioned above. The work of Torneau and Martin, and more
recently that of Fischel, has shown that spina bifida in man is not
only to be viewed as an arrest of development of the medullary

PATHOLOGY OP THE OVUM.

Fio. ISl.— Embryo 16 mm. loof, Fia. IS2.— Bscitul neotian of tha ■

■hoiruic barelip. duplseed ears, uom- bryo ahomi in Fie. 191. The eenlnl n

pluUv. uid ipiiiB bifidk. voiu gystem eonaiata Urgely of ■ mui

Fio. 193.— Section of Ihs chorionia villi of the spedoiea al:
relieulum batweea tl

240 HUMAN EMBRYOLOGY.

plate, leaving the neural tube open, but that there is also a sec-
ondary destruction of the meiubrana reuniens behind, at least in
all cases of spina bifida occulta (Figs. 188-190). Deformities of
the head, such as anencephaly (Figs. 191-193) and, what may often
follow it, cyclopia {Figs. 194 and 195), are now easily understood,
since we have the splendid experiments of Stockard and of Lewis
upon this question in Fundulus. That the great varieties of
dropsy, as pictured by Kollmann and as are frequently seen in
embryos and fetuses, are due to an impairment of the action of
the heart is now definitely proved by the enucleation experiments
of Knower. It is no longer necessary for us to seek for mechanical
obstructions which may compress the umbilical cord, such as
amniotic bands, for it is now clear that the impairment of nutri-

tion which naturally follows faulty implantation, or the various
poisons which may be in a diseased uterus, can do the whole mis-
chief. That monsters group themselves, both in nature and when
made experimentally, rather shows that certain tissues are in-
fluenced at crucial periods in their development, and not that given
substances have specific influences upon the embryo as a whole.

PATHOLOGY OP THE OVUM. 241

BIBLIOGRAPHY.

Aulfeld: Geburtshilfe, 1903.

Die Missbildungen des Menschen, Leipzig, 1880-1882.
Bardeen : Jour, of Experimental ZooL, 1907.

Ballantyne: Antenatal Pathology, 2 volumes, Edinburgh, 1904.
Bischoff: Wagner's Handworterbueh, 1842.
Born: Roux's Archiv, vol. iv, 1897.

Dareste: Recherches sur la production de monstruosites, Paris, 1891.
Driesch : Zeit. f . wiss. Zool., vol. Iv, 1892.
Eycleshymer: Amer. Jour. Anat., vol. vii, 1907.
Fischel: Ziegler's Beitrage, vol. xli, 1907.
Forster: Die Missbildungen des Menschen, Jena, 1865.
GiACOMiKi, Merkel, and Bonnet, Ergebnisse, vol. iv, 1894.
Gerlacu: Doppelmissbildungen, 1882.

Granville: Graphic Illustrations of Abortion, London, 1834.
Harrison: Amer. Jour. Anat., vol. iii, 1904.
Hertwig, 0.: Arch. f. mik. Anat., vol. xxxix, 1892; vol. xliv, 1895.

G^genbaur Festschrift, vol. ii, 1896.

Handbuch d. Vergl. u. Experiment. Entwicklg. d. Wirbeltiere, vol. L
Hegar : Monatseh. f iir Geburtskunde, vol. Ixi, 1863.
Hirst and Piersol: Human Monsters, Philadelphia.
His: Anatomie menschl. Embryonen, vol. ii, 1882.

Virchow Festschrift, vol. i, 1899.
EIelly: Operative Gynaecology, vol. ii, Philadelphia.
Knower: Anatomical Record, vol. i, 1907.
Koch: Beitrage zur Lehre von spina bifida, Kassel, 1881.
Kollmann: Archiv fiir Anat. u. Entwicklgesch., Supplement-Band, 1899.
Leopold: Arbeiten aus der dresdener Frauenklinik, vol. iv.
Leuckart: De Monstris, Gottingem, 1845.
Levy : Roux's Archiv, vol. xx, 1906.
Lewis: The Experimental Production of Cyclopia in the Fish Embryo, Anatom.

Record, vol. iii, 1908.
Loeb: Biological Lectures at Woods Holl, 1893; PflUger's Archiv, vol. liv, 1893;
ibid., vol. Iv, 1894 ; Roux's Archiv, vol. i, 1895 ; and Studies in General Physi-
ology, Chapter X, Chicago, 1905.
Mall: Welch Festschrift, Johns Hopkins Hospital Reports, vol. ix, 1900.

Vaughan Festschrift, Contributions to Medical Research, Ann Arbor, 1903.

Johns Hopkins Hospital Bulletin, 1903.

Anatomical Record, January 1, 1907.

A Study of the Causes Underlying the Origin of Human Monsters, Jour.
Morph., vol. xix, 1908 (contains a full description of all the specimens used
in this chapter).
Marchand: Missbildungen, Eulenburg's Real-Encyclopaedia, third edition, 1897,

vol. XV.

Meckel, J. F. : Handbuch d. pathol. Anatomic^ Leipzig, 1812.
Morgan : Ten Studies in Roux's Archiv, vols, xv-xix, 1902-1905.
Morgan and Tsuda: Quart. Joum. Micr. Sci., N. S., vol. xxxv, 1894.
Muller: MeckeFs Archiv, 1828.
Panum: Entstehung der Missbildungen, 1860.
Piersol: Teratolog>% Ref. Hndbk. Med. Sci., new edition, vol. vii.
Von Recklinghausen: Virch. Arch., vol. cv, 1886.
Richter: Anat. Anz., vol. iii, 1888.

Schaper: Jour. Bost. Soc. Med. Sci., 1898; and Roux's Archiv, vol. \'i.
ScHULTZE, 0. : Verhandl. d. anat. Gesellsch., 1894 ; and Roux's Archiv, vol. i, 1895.
Vol. T.— 16

242 HUIVIAN EMBRYOLOGY.

ScHWALBE, E. : Die Morphologie d. Missbildungen des Menschen und der Thiere,

Jena, part i, 1906, part ii, 1907.
Spemann : Stizungsber. d. phys.-med. Gesellsch., Wurzburg, 1900.

Ronx's Archiv, vol. xv, 1903; and Zool. Jahrbiicher, vol. vii, Supplement, 1904.
Stockakd : Roux's Archiv, vol. xxiii, 1907 ; also Jour. Elx. Zool., vol. vi, 1909.
Tarutfi: Storia delli Teratologia, 8 volumes, Bologna, 1881-1895.
ToRNEAU and Martin: Journal d'Anat. et Physiol., vol. xvii, 1881.
Tornier: Roux's Archiv, vol. xx, 1905.
Valentin: Handworterbuch d. Physiologic, vol. i, 1842.
Vejdovsky: Entwicklsg. Untersuchungen, Prag, 1890.
Voigt: Anatom. Hefte, vol. xxx, 1906.
Wetzel: Arch. f. mik. Anat., vol. xlvi, 1895.
Williams: Obstetrics, New York, 1903.
Wilson : Jour, of Morph., 1893.

Von Winckel: Ueber die Missbildung von ektopisch. entwichten Fruchten,
Wiesbaden, 1902.

Ueber die menschl. Missbildungen, Saimnl. klin. Vortrage, Leipzig, 1904.

X.

THE DEVELOPMENT OF THE INTEGUMENT.

By FELIX PINKUS op Berlin.

A. THE EPIDERMIS.

From the beginning of development the epidermis forms the
outermost investment of the body. It consists of a uniform two-
layered sheet, the upper layer forming a sort of hard covering-
layer while the lower one remains soft and gives rise to new cells
and to all the epidermal appendages of the integument. This two-
layered stage persists over most portions of the body until into
the fourth month, but even at the end of the second month it is
not altogether unmodified.

The regions which show the first signs of further development
are all upon the ventral surface of the body, the skull and back
remaining covered by an unaltered, two-layered, indifferent epi-
dermis. In an embryo of 15 mm. Kallius found the first indica-
tions of the milk ridge, and Tandler observed it later in one of the
9.75 mm. But the modifications of the epidermis are not confined
to the regions of the milk ridges at the sides of the body; also on
the ventral surface, anteriorly over the branchial arches and
posteriorly as far as the tail, changes occur which indicate a strong
formative tendency. In somewhat older stages (32 mm., 40 mm.)
an increased tendency towards development shows itself, especially
over the facial region, on the anterior surface of the face and neck
by the height and regularity of the basal columnar cells, and in the
region of the eyebrows, the upper lip, and chin by the distinct
commencement of hair formation.

a. EARLY STAGES.

Where its formation is most simple the epidermis consists of:

1. A superficial layer of flat cells, the epitrichium, or, better,
the periderm (W. Krause, 1902).

2. A layer of cells greater both in height and breadth, the
stratum germinativum (see Fig. 196).

Beneath the latter and sharply marked off from it is the
fibrous and very cellular connective tissue.

1. The periderm is the outermost layer of the epidermis. It
consists, for the most part, of flat cells, which in transverse sec-

243

244 HUMAN EMBRTOIjOGT.

tions of the integument appear to be spindle-shaped with deeply
staining, thin nuclei, while from above they appear as a layer of
large polygonal cells with large roundish nuclei. Even in very
early stages the peripheral portions of the cells flatten out, so that
only the central portions containing the nuclei remain thick (Fig.
199). Gradually they become quite flat and unusually large
(Minot, 1894). Frequently one finds some of these cells separated
from the rest, so that they are seen from the surface in transverse
sections, in which cases they appear as slightly irregular roundish
disks with centrally placed nuclei, which are either still round or
have become irregular. Around the nuclei there are frequently
a large number of roundish cavities, which ^ve to the central por-
tions of the cell the appearance of a coarse network. These are
the cells which Rosenstadt (1897) found in the beak of an embryo
chick, where they were full of large keratohyalin granules by whose
solution the cavities are formed. Zander (1886) described them
in the skin of all fingers and toes, where they were also observed
by Kolliker (vesicular cells) and
by Okamura (1900). As the
outermost layer of the epidermis
the periderm cells have the func-
tion of the later-formed corneous
layer, and they actually form an
investment of a horny character
(as shown by their reactions:
indigestibility, Unna., 1889; yel-

Fio. ISa — Uiimu fetus. S cm. in greatest i o+nininc^ wifh r»ici-ic flciH

length, female. (Collection of Prof. Roben '"W SiainiUg WlIU pitriC aClU,

Meyer. No. 249.) in.e,™entofaixiom™ right Ccdercreutz, 1907). lu the more

side; epidermiKtwo-Uyered. P.. pendemi; 5.. lav- , , , , - ... -3

erolb««lcell6;C..cori.;mwithfewcells. \200.i deVeloped pOrtlOUS Ol tlie Opider-

mis (as on the forehead) these
cells become heaped up in two or several layers, and may even
form distinct elevations, as at the nostril and mouth openings,
in which cases the cells are especially large (Fig. 198).

In man tlie periderm is not a layer which requires to be espe-
cially distinguished as the oldest or specifically embryonic invest-
ing layer. It is only the outer layer of epidermis, whose cells are
no longer turgid and have become firmer and incapable of repro-
duction. It merely occupies the place of the later homy layer and
receives additions from the subjacent germinative layer, just as
throughout life all the more superficial layers are recruited from
the deepest layer, the stratum cylindricum.

That the periderm is added to is shown
1. By the desquamation of its cells.

' Fi^. 196-198 were drnwii wilhoiit use of a i-amera and consequently the
enlarfremeiits cannot be given with certainty. The remaining: figures were drawn
with a Zeiss-Abbe camera.

Fio. 197. — Hunuui fetug. 32 mm, in gnst«at lenfth
(Collection of Prof. Robert Meyer, No. 307.) Intesument
from the right aids o( the body; (he epidermis ig becinning
to betomo three-lsyered. P., periderm; /„ sUstum bter.
medium; if., etratum germinAiivum; C, corium, rich la eelLs;

DEVELOPMENT OP THE INTEGUMENT. 245

2. By the arrangement of its cells in a regular layer, not-

withstanding the increased growth of the skin surface.

3. By the local heaping up of layers of completely and

similarly formed periderm cells in the course of
development.

Each of these three ''

phenomena indicates an
increase in the number of
periderm cells.

2. The deeper layer,
thestratumgerminativum,
is the reproducing layer
of the epidermis. Its cells
are at first low, the breadth
being equal to or even
greater than the height;
their nuclei are round or
slightly oval, stain beauti-
fully with a distinct chro-
matin network, and are
very large in proportion
to the entire volume of the
cells. The basal surfaces
of the cells, turned towards
the connective tissue, are
flat or slightly concave,
and at first are but slight-
ly connected with tlie co-
rium, so that they readily
separate in spots after the
death of the fetus (mac
eration) or as the result
of preparation. The lat-
eral walls are variou.s]y
curved, but in general
but slightly, in correspond-
ence with the pavement-
like apposition of the essentially cubical cells. The outer surfaces
are for the most part more or less convex. No special contents
can be distinguished in their protoplasm by ordinary methods of
preparation.

In those regions which already, in these early stages, show
an advance in development, the cells of the deep layer become
higher, and finally columnar; the nuclei are closer together and
form a quite regular layer, parallel with the lower surfaces of
the cells, as may be recognized by weak magnification of not too

F

10. 18S.— Th.

e man

, fetus aa I

i-ig. 197

(32 mm.)

.ht right upper lip

.. /■., p.

sride™, o

d('

lafgo veBlculi

it cell)

'. probably

;whatobli

with cells

■1;

a jera

of high

columoa'

,i(h:'«nBller.

dark

nudei; C.

lithelium. vei

■y will

.Ur: C, th.

lost layer

i.eepeci8lly.

■ieh io

nuclei. X

100.

246 HUMAN EMBRYOLOGY.

thin {15 />) sections. They stain distinctly darker and are round
or oval, the long axis being perpendicular to the surface. The
ttells are arranged palisade-like, close together, with perpendicu-
lar side walls ; and their upper surfaces are rather straight, form-
ing a slightly wavy line beneath the stratum intermedium. Their
lower surfaces are no longer smooth as in the first stage, but are
drawn out into small projecting feet. The cell bodies are much
clearer than those of the superposed layers ; they are homogeneous,
without any granular contents. Since the nuclei all lie in the
outer portions of the cells, the lower portions appear as a clear
band between the row of dark nuclei and the dense mass of nuclei
which occupies the most superficial portions of the corium.

b. FURTHER DEVELOPMENT.

Very early tiiere appears between the periderm and the
stratum germinativum a middle layer of cells, the stratum inter-
medium. Previous to its appearance the cells of the stratum
germinativum become higher and more closely approximated, and

Fio. 109. — Hurnui tctua. BS mm. verMi-bmsh lenitb, male. Epidamii dirtinoUy (brae-Uyared.
P., pcridenn with partly sBpantsd csIIb: /., stntum intenQedium: B„ ban] laygr of oelli with mitonij
C, ooriiun, rioh in celli (moatly ipi]id]»4hap«d). Mammary refioti. X 430.

their nuclei become round and large. First individual cells appear
between the two primary layers (Fig. 197), and then a complete
row of them (Fig. 199), their nuclei being small and transversely
oval and the cell bodies smaller than those of the basal cells, and
they take the nuclear stain (carmine) somewhat.

These simple conditions occur from the youngest up to rather
advanced stages of development (end of the fourth month), where
the Integument has not yet formed any special organs. In
those places where a modification occurs, as, for example, in the

DEVELOPMENT OF THE INTEGUMENT. 247

region of the mouth and nose, the epithelium assumes quite early
a very considerable thickness. Toward the end of fetal life tiie
layer (layer of prickle cells) situated between the stratum ger-
minativum and the corneous layer becomes the principal constit-
uent of the epidermis. It is a solid layer, varying in thickness in
different regions of the body, and its under surface forms an irreg-
ular network of ridges and convexities, which increase its surface
of contact with the corium from which it is nourished {rete
Malpighi). In vertical sections of the skin these ridges appear as

Fio. 200.— Huiiunfetiu.sisfath month, male. D., stratum disjunctum of the comsous l&yer; H,.
dsepsr portioD of ihe iwnieoiu Uy«r (the kentohyaliu uid eliidiu Isyen an not racofuiuible) : St.. Uyer
of prickle oella with epitlieliBi bridiei; B., Btralum (ensiiiKtivum. parUy sepanled from the cxHium and
■idi theprooeaaaa of the bual portioDsof the Bella; C., oorium. From the nght mammary recioa. Xt30.

the so-called rete papillie. The layer of prickle cells is composed
of a mosaic of closely apposed and regularly spaced large cells;
their nuclei are large, they have a polygonal outline in section,
and are variable in form and size within narrow limits (Fig. 200).
Between the layers of the two- or three-layered epidermis
epithelial bridges cannot yet be made out with certainty; but as
the epidermis increases in thickness, or in early stages where it
has already thickened, they become distinct. With ordinary stains
or when unstained they appear as prickles (Riffel, Max Schultze;
filaments d'union, Ranvier), but with specific stains {Kromayer,
Unna) they appear as epithelial fibres, which extend throughout
a whole series of cells.

248 HUirAN EMBRYOLOGY.

Tbese epithelial fibres form only in the peripberal portions of the cells;
these become denser and are distinguished as exopla^m from the endoplaem which
contains the nucleus (Studnicka, 1903). The epithelial bridges arise by the forma-
tion of vacuoles at the boundaries between cells; the fibres differentiate from the
exoplasm. In cell division the entire cell divides and both daughter cells again
form on their contact surfaces a new eaoplasm layer eontaioin^ vacuoles. In a
similar manner Ide (1889) regards the outer layer of the epidermis cells as a
membrane, the prickles being formed by a process of drawing out, as is especially
evident after division when an inter^'ening wall b formed between the two young

Almost tlie same idea, that the outer parts of the epithelial cells are a
membrane, is espressed by Unna (1903). According to his view the epithelial cells
are in close contact, the apparent clear
intervals between them (readily visible in
the case of cells rich in protoplasm) not
being intercellular spaces, but the outer
layer of the cells, which stains with diffi-
culty and is practically a membrane. The
epithelial libres are not empty spaces or
' spaces merely filled with intercellular fluid;
emi)ty spaces have a very different appear-
ance, as may be seen where the protoplasm
has retracted from around material (leu-
cocytes ) which has penetrated it. The
limits between the cells are at the so-called
nodes of Bizzostero, situated approximately
Fio. 201 .-EpitheliiU fibres and cellbridew at the middle of the epithelial bridges.
from the layer of Brickie cell?. From s poinied These nodes lie in the verv narrow clefts
^n*''l^'fib™t™;i«"h/^?^pT«m''^ between the cells and appear as nodes on
the epitheiiii cells, nodes on the intercellular acconnt of differences in refraction on
^^'tghiyZgXi.)''x1^.''i[:'r^ioS «'«*"3"S- ,1" coniification it is only this
nodes partly double. X 860. c and e, iiained membrane- 1 ike exoplasin layer that be-
with iron-hainiBtoxyliii: nodes visiWe in addi. eomes comified, and the remains of the

tion to the fibres, X 880. , . ■ . -. _c

nodes are retained on its surface.

The question wliether the nodes are
actually form elements or merely the result of light interference by superposed
networks, is not yet detinitely settled ; it would appear that the cell walls traversed
by fibres may be confused with nodes in the thin (unstained) section, for nodes are
frequently seen to be united by a narrow streak parallel to the cell wall {see Tig.
201, a.d, e).

That the epithelial fibres arise from the exoplasm is generally
admitted. They do not merely unite neighboring ceils, but may
extend through a whole series of cells. According to Schridde
(1906) certain regular fibre systems may be recognized: in the
deepest layers of the epidermis they form perpendicularly placed
ovals, which are found also in higher layers; nearer the surface
they form circles; and at the surface horizontally placed ellipses.
The form of the fibre arrangement consequently follows that of
the cells, which nearer the corium are columnar, while those higher
up are equal in all their diameters, and, finally, those at the surface
are flattened.

DEVELOPMENT OP THE INTEGUMENT. 249

c. FORMATION OF THE STRATUM CORNEUM.

Those regions in which the epidermis consists of many layers
show a comification, but also in other regions of the body there
early appear indications of it. These are distinctly visible in the
second month, and in the third month the entire skin is undergoing
comification.

Cederereutz (1907), using the method of Zilliacus, obtained the following
colorations in a fetus 3.5 cm. in length:

Yellow: the face, especially in the region around the mouth and nose (most
marked in the epithelial plugs of the nostrils) and in front of the pinna.

Yellowish: the lateral portions of the back, especially in the lower part,
and also the lateral portions of the abdomen. The arrangement of the yellow
spots on the body was rather distinctly symmetrical.

Bluish-violet: the umbilical cord, the pinna, and the fingers and toes.

In all other regions the skin assumed a dirty bluish-brownish green color.

In a fetus 5 cm. in length the entire body was distinctly colored yellow.

The pavement epithelium, which becomes yellow with this stain, picric sub-
limate, and haemalum, must be regarded as comified. Bjorkenheim (1906) has
shown that the same regions that stain yellow also resist pepsin and trypsin
digestion — a peculiarity which in the skin and mucous membranes is associated
only with comified epithelium.

The comification of the periderm, however, does not pass
through the same stages as are to be seen in the formation of the
definitive corneous layer. This is shown by the observation of
Ernst (1896), who found that in the fourth month comification
could nowhere be observed in the hand or foot, except in the nails,
by the Gram method of staining, and that a uniform corneous layer
first appeared on the toes in the sixth month.

In young embryos whose cells of the corneous layer still
retain their nuclei, keratohyalin and eleidin, which are later the
constant by-products of comification, are completely wanting.

Keratohyalin and eleidin (parakeratose) are also lacking in the adult skin
in places which comify (pathologically) in such a manner that the nuclei of the
corneous cells remain colorable with nuclear stains (haBmatoxylin, methylene blue).

These substances first appear at the end of the third month
in places where the epithelial cells are arranged in many layers.
In fetuses 10 cm. in length keratohyalin granules are rather
abundant in the face, but at this stage they are to be found else-
where on the body only in places where longer outgrowths of the
epidermis occur, as, for example, at the mouths of the long epithe-
lial appendages around the nipples, in the anlage of the mammary
gland, and, especially, in the epidermis of the nail bed. At the
beginning of the fifth month keratohyalin is still lacking in the
skin in general (Stohr, 1903) ; but trichohyalin has formed in the
hairs and keratohyalin in the epidermis of the hair follicles. With
the continued development of the skin the process of comification

250 HUMAN EMBRYOLOGY.

takes an entirely different course. The same substance that had
already appeared in the early fetal stages, although in much
smaller quantities, keratin, seems to result from the process ; but
at the surface of the skin in later stages the cornification is usually
accompanied by the formation of the by-products already men-
tioned. As a consequence the corneous layer, on account of char-
acteristic refractive properties and staining peculiarities, may be
divided from below upwards into certain readily distinguishable
layers. These are:

1. The stratum granulosum, with keratohyalin granules. The
keratohyalin (Waldeyer), in the form of round or irregularly
shaped granules (clumps, threads, occasionally bent at an angle
or branched), is situated between the nuclei and the fibrillar layer
of the epithelial cells, the exoplasma always forming an external
investment of the cells free from granules. From it and its fibrillae
the keratin is formed (Unna) ; the keratohyalin forms in the rest
of the protoplasm. That the nucleus is concerned in its formation
does not seem to be definitely shown by the similar staining prop-
erties of the keratohyalin and the nuclear chromatin, by the similar
non-polarizing refraction of the nucleus and stratum granulosum
(the layer of prickle cells, on the other hand, being doubly refrac-
tive, as well as the superficial corneous layers), and by the diminu-
tion of the nucleus as the keratohyalin increases. Arcangeli
(1908), it is true, claims to have directly observed (in the oesopha-
gus of the guinea-pig) the extrusion of keratohyalin granules from
the nucleus; and Cone (1907) has seen the same outpouchings and
expulsions of chromatin from the nucleus in human skin which
had been kept for eighteen to twenty-four hours in a thermostat
The keratohyalin is often situated at first at the periphery of the
protoplasm (Weidenreich, 1901; Apolant, 1901), but collects later
and preferably in the neighborhood of the nucleus. It is insoluble
in our hardening fluids, and especially in water, alcohol, and ether ;
but is soluble in alkalies and acids. In contrast to keratin it
is soluble in hydrochloric-pepsin. It stains deeply with nuclear
and acid stains (methyleosin. Zander, 1886; Rosenstadt, 1897;
acid fuchsin), but not with osmic acid or Sudan (Rabl, 1902).
Unna believes that with its appearance the glassy transparency
of the skin of the young fetus disappears, since the keratohyalin
(and eleidin), on account of its high refractive index, would render
the skin opaque white.

2. The stratum lucidum (Oehl's layer) with eleidin drops.
Immediately over the keratohyalin stratum is a thin layer which
also remains unstained when treated with osmic acid, but after
such treatment stains red with picrocarmine (Unna^s basal cor-
neous layer, Ranvier's stratum intermedium). Upon this there
follows a thicker layer, that blackens with osmic acid (Unna's

DEVELOPMENT OF THE INTEGUMENT. 251

superbasal corneous layer). This layer contains the eleidin, a
name proposed by Eanvier for both keratohyalin and eleidin, the
latter having been distinguished from keratohyalin by Unna and
Buzzi in 1889. Eleidin is soluble in water and, in the fresh con-
dition or after hardening, in strong alcohol; it stains with picro-
carmine and nigrosin (Buzzi). Babl (1902) regards it as softened
keratohyalin, the softening giving it the consistency of a fatty oil
(keratoeleidin). According to the microchemical investigations
of Ciliano (1908) it is an albumin. It does not appear in the
form of granules, but either as a thickish fluid extending through-
out the entire layer, or else in large drops or pools. Dreysel and
Oppler (1895) could not detect it in a five-months fetus; it was
abundant in the skin of one of eight months.

With ordinary stains or when examined unstained in glycerin
the stratum lucidum appears as a clear band. In this layer the cell
membranes are already composed of keratin.

3. The stratum corneum forms the outermost portion of the
skin. In its cells only the exoplasmic portion and the thickened
fibrillar layer are comified (Unna; Eanvier; Weidenreich, 1901),
and on their surfaces remains of the prickles can still be recog-
nized. In the cells themselves a fat which reduces osmic acid
collects and becomes very distinct in sections on treatment with
osmic acid after fixation in Miiller's fluid (Rabl, 1902) ; according
to Eanvier it has some resemblance to beeswax. The cells which
contain this substance are flat and thin, but possess the property
of swelling after an infiltrating injection of fluid into the skin.
Probably the fat (pareleidin, Weidenreich) is formed in some
way from eleidin (Rabl). Apolant (1901) assumes that the eleidin
must be expelled from the flat corneous scales which represent
completely cornified cells. The most superficial portion of the
corneous layer stains diffusely with osmic acid. It has been termed
by Eanvier the stratum disjunctum and by Unna (1883) the super-
ficial corneous layer.

In the homy substance there are two kinds of substances
which react differently to chemical reagents (Unna and Golodetz,
1908) : (1) those which are not digested by hydrochloric-pepsin
and which color red with Millon's reagent (presence of tyrosin),
but are insoluble in fuming nitric acid or in sulphuric acid +
hydrogen peroxide (keratin A) ; and (2) those which also are
undigested by hydrochloric-pepsin and stain red with Millon^s
reagent, but are soluble in the strong acids mentioned (keratin B).

d. GRANULE INCLUSIONS OF THE EPmERMAL CELLS.

While the cells, as they pass toward the surface, become
cornified and in so doing form keratohyalin, eleidin, a wax-like
substance, and tyrosin, the deeper layers contain other substances
which are not found nearer the surface.

252 HUMAN EMBEYOLOGY.

1. Pigment (melanin) occurs only in the deepest layers of
the epidermis and develops chiefly only after birth. In a six
months fetus Dreysel (1895) found no pigment; the granules
which blackened with osmic acid did so also after previous treat-
ment with chromic acid, a reaction which indicates fat but always
destroys melanin. The extra-uterine development of pigment is
much more distinct in the dark races than in Europeans. Negro
children are quite light-colored at birth; they become brownish
yellow on the second day and thereafter darken rapidly (Wieting
and Hamdy, 1907), so that in six weeks they have reached the
normal degree of darkness (Falkenstein; at four months accord-
ing to Frederic, 1905). The children of the Australian aborigines
are pale yellow with the exception of some black lines around the
mouth, eyes, and nails — but by the broadening of these lines they
become black in a few days (Gunn, according to Merkel). The
pigment of the epidermis is much more abundant than that which
occurs in the corium; indeed, the latter may be entirely lacking.
The epidermal pigment seems to be formed in situ. That it may
be formed there is shown by experiments on the adult (exposure
to Finsen light rays for two hours, accompanied by cooling and
deprivation of blood, after which treatment excised portions of
skin, examined immediately, show an increase in the amount of
pigment), by the pigmentation of skin from a cadaver (in incuba-
tor, Meirowsky, 1906, 1908), and by the pigmentation of vitiligo
spots in the absence of pigment in the corium (Buschke, 1907).
I'urthermore, the preferential presence of pigment in the skin,
chorioid, and ependjma is an indication of a special pigment-form-
ing faculty of the ectoderm ( chromatophoroma of the central
nervous system). In the epidermis the pigment granules occur:

a. In the ordinary epithelial cells, at first surrounding the
nucleus (Grund, 1905; Meirowsky, 1906, who regards the pigment
as a transformation of the nucleolar substance), but later mostly
in a cap-like mass on its outer surface.

6. In stellate cells (chromatophores), which resemble the
Langerhans cells. Whether these apparently stellate cells are
really branched or whether the processes extending out from them
are not streams of pigment granules passing out into the spaces
between the small contact surfaces of adjacent ordinary rete cells
(Rabl), is not as yet determined. According to Meirowsky 's
(1908) observations these cells develop from ordinary epidermis
cells.

The similarity of the chromatophores to the greatly branched Langerhans
cells is striking, these latter cells, as well as the fonner, being demonstrable with
especial distinctness and in large numbers by the gold and silver methods (Ramon
y CajaFs and Levaditi's silver method), so much so that on the basis of this
reaction the Langerhans cells have already and again recently been actually termed
colorless pigment cells (Schreiber and Schneider, 190S; Bizzozero, 1908). The

DEVELOPMENT OF THE INTEGUMENT. 253

questions in discussion turn upon whether the epithelium always forms pigment in
situ (Post, 1893, the development of feathers; Jarisch, 1892, no pigment in the
hair papillee; Sehwalbe, 1893, the change of hair coat in the ermine, in which the
white winter coat contains no pigment, while the summer coat makes its appearance
pigmented; Rosentadt, 1897), whether the epithelium also forms the spider-like
cells (melanoblasts) (Grund, 1905; L. Loeb, 1898; Wieting and Hamdy, 1904, the
gradual pigmentation of the nose in new-bom dogs), which then may wander from
the epidermis into the cutis (pigment stored up in the lymph-nodes, shown by
Jadassohn, 1892, in pityriasis rubra and by Schmorl, 1893, in the negro), or
whether the chromatophores are originally pigmented connective-tissue cells which
wander into the epidermis and supply its cells with pigment (Ehrmann, 1896; in
the unpigmented egg of the triton there is formed in the mesenchyme, when the
development of the blood begins, a series of dark cells, melanoblasts, which later
become rich in pigment granules and give rise to all the pigment in the body. No
pigment is formed in the epithelium, it is carried there by the melanoblasts; they
appear about the hair anlagen at an early period, even before the formation of
the papillae). According to all recent works the idea that pigment is formed in
the epidermis itself seems to be well founded.

2. Glycogen is abundantly present in the embryonic epidermis
(S. H. Gage, 1906). After the sixth month it diminishes in quan-
tity and is finally to be found only in the cells in which it occurs
in the adult (Lombardo, 1907). The epithelium of the sudoripa-
rous glands, especially, regularly contains glycogen, the more the
more actively they are secreting; furthermore, the outer root
sheath of the growing hair, from the bulb to the insertion of the
muscle, contains it, while in that of the bulb hairs it is wanting
(Brunner, 1906; Lombardo).

3. Fat is especially evident in the basal columnar cells and in
the stratum granulosum even from the fifth month. The layer of
prickle cells which intervenes between these is practically fat-free,
its fat having presumably been used up during the divisions of the
cells. As evidence for the absence of fat in the prickle cells it
may be stated that post mortem no fat appears in them when they
are placed in a thermostat, while in twenty-four to seventy-two
hours the quantity of it in the stratum cylindricum and stratum
granulosum is greatly increased (Cone, 1907). In the layer of
columnar cells the fat, made evident by fettponceau, surrounds the
nudeus in the form of granules of varying size (up to one-quarter
the size of the nucleus) and streams out toward the periphery of
the cells. In the stratum granulosum it is equally distributed
from the cell periphery to the edge of the nuclear cavity, some
loops lying even within this (according to Unna it is completely
filled by a fat drop). Much fat is also present in the stratum
lucidum, where it is more irregular both in form and distribution
than in the stratum granulosum. In the actual stratum comeum
it lies especially between the cells.

In between the epithelial cells processes of branched con-
nective-tissue cells filled with fat granules (lipophores, Albreeht)
extend from below.

254 HUMAN EMBRYOLOGY.

B. CORIUM.

The connective-tissue portion of the skin, the corium, is de-
veloped from the most superficial portions of the somites. Ven-
trally it arises from the outer part of the dermomuscular plate
and is applied to the myotomes so that, together with the epider-
mis, it sinks down into the furrows between successive myotomes
(sub-epithelial segments, Osc. Schultze, 1897). The case is similar
dorsally, where the segmental furrows are continued between the
sclerotomes which surround the spinal cord. The segmental fur-
rows, however, soon disappear. The corium or dermis is at first
very cellular, and the two portions into which it later divides, the
corium proper and the subcutaneous fascia (tela subcutanea), are
not distinguishable in the second month. Its oval cells elongate
and begin to form fibrils (observed by Spalteholz, 1906, in the fifth
week) in their own protoplasm, and these soon anastomose and
form a delicate, somewhat irregular network, which, according to
Spalteholz, remains throughout life unsheathed by the protoplasm
mass and in connection with its original cells. A regular arrange-
ment of the bundles of fibrils makes its appearance at about the
end of the third month. In embryos 7-8 cm. in length the bundles
arrange themselves in the lower part of the body in parallel bands
running around the body (a result of the stretching of the skin
by the growing liver). A little later the parallel arrangement of
the bundles appears in the remaining portions of the skin as a
result of the tension produced in it by growth (Otto Burkard,
1903). The regularity of the fibrils is interfered with by the
development of the hairs (from the fourth month onwards), since
the bundles separate around the down-growing hairs and form
meshes, which after certain modifications are transformed into
Langer's (1861) rhomboidal meshes.

In the later embryonic period the superficial layer of the
corium separates into the papillary bodies and the stratum retic-
ulare. The papillary bodies form a superficial layer whose fibres
— collagenous connective tissue — stain reddish with Van Gieson's
stain (picric acid and acid fuchsin) and are arranged horizontally,
but with many vertical fibres that extend to the boundary of the
epidermis.

The stratum reticulare consists of coarse and fine bundles of
connective-tissue fibres, which, interwoven, run more or less
parallel to the surface of the skin and take the picric acid of Van
Gieson's stain somewhat more strongly. The varieties of fibres
which can be clearly distinguished microchemically diflferentiate
rather early in certain regions of the body. According to earlier
accounts the elastic fibres of the corium first appear in the seventh
or eighth month, but according to Spalteholz (1906) they are pres-
ent in the truncus arteriosus of the chick even in the third day, in

DEVELOPMENT OF THE INTEGUMENT. 255

pig embryos of 9.2 mm., and in calf embryos (in the ligamentmn
nuehae) of 35 nam. They arise intracellularly, either directly as
fibres without any granular prophases in the protoplasm of the
cells (Spalteholz; Gemmill, 1906, in tendons; Schiffmann, 1903),
or as rows of granules (Jones, 1907, in the epicardium of chick
embryos ; Teuff el, in the fetal lung ; Nakai, 1905, in the vessels of
chick embryos). The elastic substance can, apparently, form in.
all fibroblasts; special elastoblasts (Passarge, 1894; Loisel, 1897)
are not recognizable.

Pigment cells occur in the corium in varying numbers; they
are partly small, like the epithelial chromatophores, partly espe-
cially large and deeply seated. These latter appear during the
fourth fetal month. According to Grimm (1895) and Adachi
(1902) they are the cells which produce the blue gluteal spots
(Mongolian spots). The corium pigment appears to be formed
in the connective-tissue cells themselves, as the result of activities
by which pigment is produced from uncolored constituents (accord-
ing to Meirowsky, 1908, the cell nuclei are concerned in the process ;
extruded nucleoli are transformed into pigment).

The young, richly cellular corium contains wide blood-vessels
with a distinct endothelium, but without any of the other con-
stituents of the wall. Gradually the abundant and specialized vas-
cular supply of the skin of the child develops, with its superficial
vascular network and a deeper one parallel with the surface of the
skin and connected with the superficial network by vertical
branches, and with the vascular supply to the glands and hairs and
some superficial fat islands.

Beneath the corium is a looser tissue characterized by the
formation of fat islands. According to Toldt these begin to form
at definite places, so that the fat lobe is a special organ, with a
peculiar blood-supply — a view with which, according to Rabl
(1902), the sharp delimitation of the fat lobes is in agreement.
More generally accepted is the idea, first suggested by Czajewicz
(1866) and later more definitely by Hemming (1876), that in the
subcutaneous tissue every cell may become a fat cell, even although
there are constant areas in which fat develops by preference
(Unna, 1881). The cells are at first branched and contain the fat
in the form of small droplets, from which larger drops are formed,
while the processes of the cells become less distinct. Gradually a
large fat drop is formed, surrounded by a thin layer of protoplasm
which contains the nucleus. The fat cells lie in groups, surrounded
by ordinary connective tissue and richly supplied with blood-
vessels. The masses of fat assume various forms, such as lobes
into which the principal blood-vessel enters from below, cords
extending along the blood-vessels, or islands standing isolated on
the blood-vessels of the hair follicles and lacking a special vessel.

256 HUMAN EMBEYOLOGY.

With the modem fat stains (fettponceau) it is possible to find
even in the adult skin branched fat cells packed with small and
large drops, whose processes extend into the epidermis (near to
which they usually lie). These are Albrecht's lipophores (Cone,
1907). Fat granules may also be detected by staining in cells
with pigment granules and in those with enzyme granules.

C. THE CONNECTION BETWEEN THE CORIUM

AND EPIDERMIS.

The two-layered epidermis lies flat upon the corium through-
out the greater portion of the body. In those places where the
basal layer consists of high colunmar cells, even in early stages
(30 mm.) a closer connection occurs, the bases of the epidermal
cells being divided into fine processes which fit into corresponding
depressions of the corium. With increasing growth this connection
becomes continually more intimate, and in fetuses of 10 cm. the
basal portions of the columnar cells consist of a finely fibred
protoplasm, which stains deeply and represents the rooting feet
of the epidermis cells, firmly connected with the especially cellular
surface of the dermis. This condition becomes more marked with
increasing growth. In the adult skin the central parts especially
of the cell bases seem to have formed fibrous processes. By
maceration in 10 per cent, salt solution (Merk, 1904), in pyro-
ligneous acid (Loewy), or in weak acetic acid (Blaschko, 1888)
the epidermis separates from the corium without losing its own
continuity, so that it seems that a change in the arrangement of
the protoplasm of the foot portions of the epidermal cells has
occurred (Merk), a change which is also indicated by their dif-
ferent staining properties (bright red with eosin; reddish yellow
with picric-acid-fuchsin, in contrast with the yellow color of the
rest of the cell, a darker brown than the epithelial cells with
saffranin after fixation in Flemming's fluid ; a brown or grey color,
the epithelium remaining uncolored, with the elastic fibril stain
of Unna and Weigert, Rabl, 1902). Quite as delicate as the fibre
structure of the epithelial root feet is that of the subjacent super-
ficial layers of the corium. But while the former are arranged
perpendicular to the surface, in correspondence with the arrange-
ment of their fibrils (epithelial fibres), the delicate fibrillation of
the corium is, in general, parallel with the surface, only the finest
of connective-tissue and elastic fibres ascending vertically towards
the epithelium boundary. A penetration of corium fibres into the
epidermis cannot be made out, but whether basal epithelial cells
separate from the epidermis and wander into the corium or not is
less certain. According to Kromayer (1905, dermoplasia), and
especially according to Retterer (1904), the superficial portion of

DEVELOPMENT OP THE INTEGUMENT. 257

the corium is of epithelial origin, being foi-med by cells separated
from the epidermis; and recently Krauss (1906), as the result of
the employment of an especially distinctive staining method, ha3
regarded a portion of the corium in the Reptilia as derived from
the epidermis. On account of the irregularity of the contact sur-
face between the epidermis and the corium, even the thinnest sec-
tions are more or less oblique and give the appearance of an inter-
stratification of the deepest portions of the epithelium and the
connective-tissue fibres (the elastic fibres, namely), and so of the
penetration of the fibres into the epithelium. So extensive a
migration of epithelial cells and their conversion into connective-
tissue cells has certainly not been demonstrated. A certain
mingling in the course of development of living epithelial elements,
such as touch corpuscles, pigment cells, and perhaps also un-
pigmented naevus cells, with corium constituents has been observed
by many authors. In pathological processes separated epithelial
cells (as in lichen ruber and vesicular eruptions) or epithelial
islands or appendages (as in tuberculosis and trauma) usually
gradually degenerate and only rarely find opportunities for further
growth ; when they do so the growth is always of an epithelial form
(traumatic epithelial cysts, milia).

The connection of the epidermis and corium, notwithstanding the ease with
which they may be separated by maceration, is exceptionally intimate and is not
broken by the displacements of the integument which occur in the course of normal
development. The epidermis follows every outgrowth of the corium and the latter
yields to every epithelial projection, closely surrounding it on all sides. Since the
epidermis and superficial corium (in later stages separable into the papillary
bodies and the subpapillary layer) constitute anatomically a single tissue-mass,
and also are exposed in common to all changes, physiological and pathological,
Kromayer (1899) has united them under the term parenchyma skin.

D. DERMAL RIDGES AND FOLDS.
DERMAL RroOES PRODUCED BY SURFACE GROWTH, GROWTH FOLDS.

For a long time the under surface of the epidermis remains
smooth or slightly and irregularly wavy. With the development
of hairs on the eyebrows and lips in the second month its first deep
ingrowths into the corium occur. Much later, when the rest of
ihe hair has begun to form everj^where, the lower surface of the
epidermis begins to increase in certain regions, the rete ridges
begin to form on the palms of the hands and the soles of the feet,
and some time after these the more delicate outgrowths which form
the papillary bodies and the rete Malpighi appear. The rete
ridges make their appearance on the previously formed touch
balls (see Figs. 73, 76, 77, and 78, p. 87-89). Each terminal phalanx
of the fingers and toes bears one of these, four occupy the inter-
digital spaces between the heads of the metacarpal and metatarsal

Vol. I,— 17

258 HUMAN EMBRYOLOGY.

bones, and one corresponds to each of the lateral swellings of the
hand and one to the side of the little toe. These are recognizable
after the sixth week and reach their greatest relative development
in the fifteenth week. After that they begin to disappear and their
place is taken by corresponding systems of papillary ridges (papil-
lary ridge patterns, which have a triradiate form, consisting of
three lines arranged in the form of a triangle, with diverging lines
from each single, Schlaginhaufen, 1905; Whipple, 1904). In the
eighth week (Evatt, 1907), in fetuses of 3-4 cm. (Wilson, 1880),
the epidermis lies flat on the corium and is separable by slight
maceration; no trace of ridges is visible. In the eleventh week
(Evatt), in fetuses of 9 cm. (Wilson), the skin appears streaked
when seen from the surface, showing alternating light and dark
lines, the beginnings of the formation of the rete ridges.

While the outer surface of the epidermis is still smooth, with-
out any pattern, there arise on its lower surface simple ridges, that
are triangular in section with the apex directed downwards. They
produce the striated appearance of the skin and are Blaschko's
gland ridges, the sudoriparous glands forming later on their lower
angles. The outer surface is not raised into corresponding ridges ;
rather it may show grooves (W. Krause, 1902). Only in the
eighteenth week do ridge- like elevations of tlie outer surface ap-
pear, one corresponding to each of those on the lower surface.
The development of the ridges begins at the tips of the fingers and
toes and proceeds proximally over the entire surface (not radially
from a centre), at the same time producing the ridge patterns with
their whorls and spirals. These patterns even in this early stage
show the same individual differences as may be observed in adults,
and tliis is so even before the ridges of the outer surface are
formed. First the gland ridges are formed and then the sudori-
parous glands begin to form from them. At about the same time
tlie same process takes place in the palm of the hand. In the cases
of the gland ridges (papillary ridges, Hepburn; epidermic ridges^
Whipple, 1904) an epithelial elevation of the outer surface (crista
epidermidis superficialis, Heidenhain, 1906) corresponds to an
epidermal ridge of the under surface (crista epidermidis pro-
funda intermedia, Heidenhain; subdermal ridge, Evatt, 1907). At
regular intervals sudoriparous glands arise from them, their ducts
later traversing them in a cork-screw fashion to reach the exterior.
Then a second series of lower ridges, destitute of glands, is inter-
posed between the ^land ridges, forming Blaschko's folds (crista
epidermidis profundaB limitantes, Heidenhain) ; and finally delicate
low transverse bridges are formed between the two series. Cor-
responding to the folds on the outer surface-, and therefore cor-
responding to the grooves between the ridges, are depressions of
the epidermis (sulci superficiales, Heidenhain).

DEVELOPMENT OF THE INTEGUMENT. 259

According to Whipple (1904) the gland ridges are formed by
the union of isolated epithelial papillae, each of which is traversed
by a sudoriparous gland ; and the transition of a ridge into a series
of such papillae with few or but one gland duct is also to be seen
in certain regions of the adult skin, constantly on the radial sides
of the fingers and especially of the index finger. The development
of the ridges on the palms and soles is completed at the end of the
fifth month. From them there arise as secondary outgrowths the
rete papillae, between which the true papillary bodies occur. In
extra-uterine life the ridges lose much of their regularity, since
new irregularly arranged outgrowths make their appearance.

Simultaneously with the formation of the rete ridges the outer
surface of the corium develops elevations and papillae, as a nega-
tive, as it were, of the epidermis ; for, on account of the continuity
of the entire parenchyma skin, an elevation of the epidermis must
produce a practically corresponding depression of the corium.
The dermal ridges of the hands and feet, so far as these are not
movement folds but are the result of the enlargement of the epi-
dermis surface (Lewinski, 1883), have their arrangement deter-
mined by a series of mechanical conditions. In general, they are
arranged transversely to the direction of the limb in grasping or
progressing (friction skin, Whipple) and, consequently, at right
angles to the directions of the most delicate sensations for the
substratum (Schlaginhaufen; their distally overlapping, imbri-
cated arrangement at the tips of the fingers, pointed out by Kidd,
1905, also serves to increase sensation) ; they constitute neutral
curves, so that they are neither stretched nor compressed by ten-
sions of the surface, and, consequently, the touch sensation is not
disturbed by the sensation of a surface tension (Kolosoff and
•Pankul, 1906).

In the regions of the body where hair occurs, longer or shorter
meshed networks form between the hairs ; the rete papillae become
much lower in the vicinity of the hairs, so that these, when fully
developed, occupy the centre of a star of low rete papillae, which
extend more or less distinctly upon the hair follicle (Philippson,
1906).

As a result of the formation of the papillae of the corium and
of the ridges and papillae of the epidermis, the under surface of
the latter becomes greatly increased in comparison with its earlier
smooth condition, and a very much greater nutritive and functional
surface is thus secured for the epidermis. The rete ridges follow
in general the tension lines of the skin, so that a correspondence
exists between the tension lines and the development of the ridges.

260 HUMAN EMBRYOLOGY.

TENSION FOLDS.

In addition to the folds produced by the development of the
skin — the growth folds — a second variety occurs, produced by the
innumerable repeated bendings and foldings of the skin during
movements of the parts (Lewinsky, 1883; Blaschko, 1888; Loewj^),
or by the strains resulting from these movements (Philippson,
1889; distention folds, Charpy, 1905). In the palm of the hand,
where the system of growth folds is most marked, some of the
strongest flexion folds have the same direction; but elsewhere a
contrast between the two systems seems to exist in that, in parts
with strong flexion folds (joints, hands, nape), these cross the
lines of tension of the connective-tissue bundles at right angles.
The tension of the tissue is the cause of Langer's lines, the connec-
tions between the slit-like clefts formed when the skin of the
cadaver is pierced by a round instrument. With these also cor-
respond, in addition to the rete ridges, the arrangement of the
hairs. The investigation of the tension lines shows that in the
fetus great displacements of the skin occur during the course of
development.

At first no directions of cleavage can be distinguished in the
skin, the tensions to which it is subjected being equal in all direc-
tions ; but with the commencement of the parallel arrangement of
the connective-tissue bundles there arises a definite cleavage (Otto
Burkard, 1903). The cleavage lines pass transversely from the
dorsum ventrally, diverging, accordingly, ventrally; in the ex-
tremities they run longitudinally. This cleavage arises gradually,
those portions of the skin that are more strongly stretched by the
growth of the deeper parts showing it at an earlier period than
those parts in which the conditions of tension are indifferent.
It begins in the third month and lasts until the end of the fourth
or the beginning of the fifth. By the formation of the hair in the
fourth month, the originally parallel bundles of connective tissue
become arranged so as to form rhombic meshes, and then suddenly
rearrange themselves as a result of the hair development in the
fifth month, so that their new arrangement is at right angles to
the original one and the cleavage lines become longitudinal in the
trunk and circular on the arms though less so on the legs. The
gluteal region now shows cleavage for the first time, the lines run-
ning circularly and diverging from the gluteal cleft. In the neck
they run horizontally around and remain thus until the adult con-
dition, in which they run horizontally from the occipital region to
the thorax. Transitions between the courses of the first cleavage
lines and the second do not occur. It is not a question of a gradual
development as the result of growth processes, but of a very rapid
rearrangement of the originally transversely directed rhombic

k.

DEVELOPMENT OF THE INTEGUMENT. 261

meshes into longitudinally directed ones, with a brief intervening
stage in which the meshes are quadrate and in which no definite
Unes of cleavage occur.

These second cleavage lines vanish in the fifth and the begin-
ning of the sixth month and gradually become horizontal, return-
ing to the primary direction and being at right angles to the
secondary one. This change is the result of gradual growth dis-
placements (growth in length) and from it there gradually de-
velop the oblique cleavage lines of the adult, directed from above
downwards. The cleavage lines of the head and face change but
little during development. (See representation by Otto Burkard,
1903.)

E. THE METAMERISM OF THE SKIN.

The segmental plan upon which the human body is constructed
suggests that a metameric arrangement exists also in the skin
(Blaschko, 1888). In some mammals (mouse, pig, rabbit), and
also in man, the skin in early stages of development follows the
metameric arrangement of the underljdng structures with which
it is connected (the myotomes ventrally and the sclerotomes dor-
sally, 0. Schultze, 1897) ; this is the subepithelial segmentation.

In fishes the segmental arrangement of pigment cells (Bolk, 1906) indicates
such a metamerism of the skin. In mammals none of the well-known metameric
markings (such as those of young animals, the zebra and tiger), nor yet the
metameric arrangement of the hair (trichomerism, Haacke), nor the circular
arrangement of scales on the trunk and tail, can with certainty be referred to a
primary metamerism of the skin. That this may exist, however, although invisible
to our eyes, is indicated by pathological conditions, which are only to be explained
as due to a certain predisposition to disease of growth zones or their boundaries
(naBvi, linear inflammations). The method of investigation that represents to us
the development of skin segments is the comparison of the course of development
of the peripheral nerves with that of the skin areas which they supply. No other
tissue, neither the skeleton nor the musculature, corresponds with the segmental
structure of the skin. Even the blood-vessels are less satisfactory in this respect;
for the blood follows the most convenient paths it can find. The blood-vessels
accompany the nerves and frequently confuse, by their anastomoses, the distinct
metameric course maintained by the nerves.

The nerve connection between the skin and the spinal cord is established in
early stages, and it may be supposed that it remains unchanged until the com-
pletion of development in spite of all displacements and modifications dependent
on growth. Those portions of the skin which are supplied, for instance, by the
sixth and seventh thoracic nerves, and which Grosser and Frohlich (1902) have
followed throughout the development from an embryo of 14i mm. onwards, are
to be regarded as identical in both the fetus and the adult.

The territory which is supplied by a definite segmental spinal
nerve remains the same from the beginning to the end and is known
as a dermatome. At first the dermatomes form rings around the
body, narrower ventrally and broader dorsally, in correspondence
with the curvature of the embryo, in which the thorax and abdomen

262 HUMAN EMBRYOLOGY.

are much shorter than the back. The spinal cord at first grows
more rapidly than the skin, and the lagging behind of the latter is
shown by the fact tliat the cutaneous nerve branches pass
proximally from, for example, an intercostal trunk, in order to
reach their cutaneous areas. They are held back because their
areas of distribution are of slower growth than the spinal cord.
Later on the spinal cord lags behind, and the skin, with the out-
growths of the arms and legs, grows more quickly, drawing the
nerves peripherally with it. The growth of the extremities draws
the skin out, and the more distant cutaneous areas of the trimk
must follow towards the region from which the limbs arise. The
dissection of the nerves (Voigt, 1857) shows the situation of the
corresponding skin areas, wliich are to be regarded as skin meta-
meres. In spite of all displacements, such as occur, for example,
in the extremities, the common supply of an area of skin by the
branches of the metameric nerve indicates its individuality (Head,
1898; Sherrington, 1893; Seiflfer, 1898); and comparative studies
(Grosser and Frohlich, 1902, 1904) show that it is to be regarded
as a genetic anlage (dermatome).

The conditions are much the clearest in the trimk, although
even in this region great displacements occur. To the skin pass :

1. Twigs of the ramus posterior of each spinal nerve, the
medial twigs in the upper regions and the lateral in the lower.
Both pass downwards from the intravertebral foramen on their
way to the skin, the medial (upper) ones to a lesser extent than the
lower (lateral), which occasionally descend rapidly over three to
four rib regions, since their cutaneous areas have been drawn
downwards to this extent by the development of the lower limbs.

2. The rami laterales and the rami mediales are carried out
of their original course, parallel to the ribs, to a much smaller
extent. On the ventral surface of the bodv the skin follows more
regularly the growth of the deeper parts ; it is drawn downwards
to a certain extent, but at the same time the ribs and the greatly
enlarged abdominal wall are also displaced caudally. The skin
and the deeper parts have a common growth and retain their rela-
tive positions.

F. THE HAIR.

The development of the hair begins on the eyebrows, the upper
lip, and chin at the end of the second month. On the eyebrows it
has been seen in fetuses of 27 mm. (Keibel and Elze, ^^Normen-
tafel," No. 80, 1908), but the number of anlagen was still very
small. In a fetus 32 mm. in its greatest length (No. 307 of the
collection of Professor Robert Meyer) I found on the eyebrows
89 anlagen on the left and 81 on the right; on the upper lip 73
anlagen on the left and 57 on the right; on the chin only one of
which I could be certain and several uncertain ones.

DEVELOPMENT OF THE INTEGUMENT. 263

In another fetus 30 mm. in length (No. 310 of the same collec-
tion) the anlagen were somewliat more numerous and to a certain
extent further advanced in development. At this time hair anlagen
are present in no other regions.

The general hair coat begins to form at the beginning of the
fourth month, and at this time only the earliest anlagen occur,
except in the face region, where they already show a more ad-
vanced development. On the body the anlagen are quite closely
placed, on the head they are somwhat further apart, and on the
face they are especially close, being arranged laterally on the upper
lip in a row which at places is unbroken. The hairs arise singly,
but in many regions another appears early on each side of the first-
formed hair, so that groups of three are formed. Stohr (1907)
saw on the back of the neck two additional hair follicles sprouting
out beside a regularly arranged hair group, but the nature of these
could not be determined on account of their slight development.

The phylogenetic origin of the hairs has not yet been definitely ascertained.
Certain facts in connection with their structure and arrangement have, however,
been taken as the basis for theories whereby the mode of formation of the hair
might be explained. Of these theories the two most importaiit are the following:

1. Maurer's theory of the origin of hairs from the epithelial sense organs
(lateral-line organs) of the Amphibia ( Stegocephali ) is based upon the similarity
of these organs to the first epitlielial hair anlagen (hair germs) and upon the
comparable arrangement of the sensory hairs (sinus hairs) of the mammals and
the lateral-line organs of the head in fish and Amphibia. It explains, according
to Maurer, all the conditions of the evolution of the hairs. The transverse rows
of hair groups, which are of the greatest importance for the following theory,
constitute merely a topographic arrangement, and are independent of the airange-
ment of the scutes of the Stegocephali.

2. Weber^s theory of the identity of the scutes of mammals with those of
their reptilian ancestors (1893), a theory which has been further worked out by
Reh (1896) and De Meijere (1894). As the type of the hair arrangement rows
of hairs standing in groups of three have been taken, the groups in successive
rows frequently alternating regularly (quincunxial arrangement). This plan is
shown in the development of the hairs at the posterior margin of regularly
arranged scutes (supposed to represent the scutes of the Promammalia). The coat
of the most thickly covered mammals is denved from the groups-of -three arrange-
ment by secondary hair formations, which are usually recognizable in the embryo,
or by the arrangement of the hair muscles and the sudoriparous glands. The liair
groups belong genetically to the scutes, behind (De Meijere), or, better, upon
(Reh), which they arise. This theory receives support from my discovery of the
hair disks, in case these may be identified with the touch spots of the reptilian
scutes. Just as the reptilian and stegocephalan scutes are bilaterally symmetrical
structures, whose planes of symmetiy correspond with the longitudinal axes of
the trunk or the extremities, so, too, each skin area which is regarded as belonging
to a group of three hairs is to be regarded as a bilaterally symmetrical structure
from its first beginning, the middle hair of each group of three being situated in
its longitudinal axis and being flanked on either side by the two additional hairs, or
by all the additional hairs when the group consists of more than three; on the
posterior surface of the hairs it has associated with it the sebaceous gland, the
sudoriparous gland, the muscle, and the hair plate, the whole fonning a hair terri-

264 HUMAN EMBRYOLOGY.

tory which must be regarded as coiTesponding to a scute of the promammaliau
integument. According lo this theory tlie hairs are to be regarded as Dew acqui-
sitions by the Mammalia, if the entire scute did not in much earlier periods surround
a lateral -line organ. Such a condition would be analogous with wbat occurs in the
fishes, in which the scales of the lateral line also bear the lateral-Hue organs, and
it would render possible a union of the present tlieory with that of Maurer.

As the first aniage of a hair, in small areas of the three-layered
epidermis the nuclei of the columnar cells become higher and more
closely packed, so that more cells rest upon a given area of the
corium surface than is the case elsewhere (Fig. :i02, primary hair
germ). In addition, there may perhaps be a very slight downward
convexity of the germ, but the nuclei of the corium usually do not
show any increase in number.
These structures are rather
uncommon ; they seem to
rejjresent a very transitory
stage, and only when they
occur among more developed
hair anlngen can they be re-
cognized as the first stage of
these. A similar appearance
is presented by marginal sec-
tions through structures!
which are distinctly hair
-t human fetus. 8.6 genos (Stohr, 1903) and they
XMribS™ppm'^ must not be confounded with
^"'n''Vumb^Ts"nd thcsc. Tlicy correspond in size
thB™iinoinjre«Mofthe™ii«tive-u89ueceii.of the ^jth the hair gcrms, mcasur-
""""' ing 45-6(1 ft in diameter. The

hair germ (Fig. 203) differs from them in the distinct bulging
out of the layer of columnar cells towards the corium. The nuclei
of the columnar cells are arranged radially to a somewhat distant
centre, and are frequently slightly curved so as to be concave
toward the centre of the structure (Maurer, 1895, the kiln-like
arrangement of the hair cells). At tlie point toward which the
cells converge there is occasionally a roundish opening. Even in
this early stage the germs do not possess a radial structure, but
are bilaterally symmetrical (Figs. 204 and 205). On one side
(the side of the later acute angle between the hair follicle and
the under surface of the epidermis, the anterior surface of the
hair) the columnar cells come quite up to the hair germ; on the
other side (the posterior surface of the hair) lower cells occur in
its neighborhood (Stohr's anlage of the hair canal). The kiln-
shaped anlage is covered by some cells placed horizontally. The
corium beneath the columnar cells, which are increasing in height,
usually contains more nuclei than are present in yet undiffer-

DEVELOPMENT OF THE INTEGUMENT. 265

entiated regions, and beneath many hair anlagen the increase of
the nuclei is especially pronounced (anlage of the papilla). No
differences seem to exist between the early formed hair anlagen
of the face and head and those of other portions of the body.

Flo. 204. — LoD^tudinol section ofa hair (emi of SDOther S.A<»d, human fetus, more advanral t1
H.-Kan.. hair canal cells (Siflhr). Spaces exist amoDi the oeUa of tbe lerm. V.. auterior turface;
posterior gurface of the hair germ. X 430.

uul (he kiln-like arranien

Witli the further development of the hair germ Stohr's stage of
the hair papilla is reached, in which the hair anlage, while retaining
approximately its original diameter, gradually grows downward
into the corium (Fig. 206). The hair papilla projects downward
from the stratum cylindrieum; it consists of an outer layer of

266 HUMAN EMBRYOLOCy.

cylinder cells, which are already beginning to differentiate in the
deeper parts of the follicle, and of polygonal cells, arranged more
irregularly, which fill the space
bounded by the oolumnar layer.
,. The latter, when the length of the
hair papilla is about three times
its breadth, shows on the posterior
surface two low outgrowths with
outwardly diverging, regularly
J arranged nuclei. The upi>er of

these is the aniage of tlie sebaceous
gland, which in rare instances
may be double (one above the
other, Diem, liK)7) ; the lower one
is tliat of tlie sweltiug (hair bed,
Unna, 1883), which, usually, be-
coming lower, extends around to
the anterior surface of the follicle.
The lowest portion of tlie hair pa-
pilla consists of high columnar
cells arranged in a kiln-like man-
ner and forming a convexity which

th* fetus of rig?. 202 203. unfl 205. «.. hnir 1" Illglier lUaU Uldl Ol UlC bllUl-

m»irixwiih>ti««-.oiti,««,nver^nBpointo(ihf j^rly arranged cells of the hair

miitnx «1U; Pa., anlngc of pBpiIln: Hbg.. ron- •' . ■ i . n ■ i ant V

nective-tL-™eh>irBh«th;B;..ve'icui«r(Kii,ot germ (nuitrix plate, Gaicia, 1891).

*ute;'*H!^rt?|i».(«VioTsurfa«™IIhThe'<™»"^ There is also occasionally to be

n^'^^"'a^D"^X'n^>^oTii^'hl!^ found in this region, at the point

nrdimj?. >: 430. toward whicli the cells of the

nto the bulb papilli. Pa., biiIbcp ot
lir canal wlln: //.-K„ luigential MC-
et HiHtolov«, Fig. 300; EntwickluDS

DEVELOPMENT OF THE INTEGUMENT. 267

matrix converge, a roundish cavity (Fig. 206). The under surface
of the hair papilla is flattened or even somewhat concave. The
epidermis in front of the hair is unmodified and three-layered,
consisting of periderm, stratum intermedium, and stratum cylin-
dricum; the posterior surface consists of proliferated, flatter, and
elongated cells (the hair-canal anlage), which in part already show
a beginning cornification (Stohr). The hair papilla is enclosed
laterally within a layer of connective tissue with numerous cells.
On the under surface this is continued into a mass of cells with
perpendicularly arranged, concave nuclei, the concavity looking
upwards, which are immediately adjacent to the matrix (connec-
tive-tissue papilla). All these peculiarities of the hair papilla may
be more or less pronounced. Thus a very distinct swelling may
occur on one which does not show any marked apical flattening;
or on a very short epidermal papilla there may be a distinct
connective-tissue one, or vice versa. Further, in these early stages
there may be opposite the swelling a marked aggregation of nuclei,
which is to be regarded as the anlage of the rnuscidus arrector pili
(Stohr). The hair anlagen, almost two months old, on the brows
and lips have not advanced beyond this stage when the formation
of the anlagen of the general hair coat begins. Some similar
structures (gland anlagen) are aJone larger; these will be con-
sidered in connection with tlie perimammillary epithelial appen-
dages.

In the further course of development the layers of the hair
and its sheath begin to form (Fig. 208). The epithelial papilla
grows longer and thicker below (the bulb-papilla stage, Stohr).
Its anterior surface abuts upon thin unaltered epidermis, while the
posterior is continuous with the anlage of the hair canal, already
recognizable in the two yoimger stages. This assumes the form
of an elongated, partly comified mass of flat cells, projecting from
the under surface of the epidermis behind the hair. The epithelial
papilla is still surrounded by a high columnar epithelium, which
at two regions on the posterior surface, that of the sebaceous gland
above and that of the hair swelling below, projects more markedly
than formerly. The anlage of the sebaceous gland does not always
lie exactly in the posterior surface of the hair ; occasionally it lies
more laterally and later may surround the entire periphery of
the hair or come to be principally lateral or anterior to it. The
specific fat formation begins at an early period in the central
cells. The under surface of the epidermal papilla or bulb is at
first only slightly concave for the reception of the connective-tissue
papilla, but later (apparently very quickly, Stohr) it becomes
deeply concave. The high columnar cells which line the concavity,
the matrix plate, become the source of an upwardly projecting,
conical, pointed mass of cells (the hair cone), which extends up-

268 HUMAN EMBRYOLOGY.

wards into the still rather irregularly arranged cell material in
the interior of the follicle. The outer boundary of this cone is
formed by a layer of ceils {the anlage of Henle's sheath), which
extends from the point where the outer surface of the follicle
bends into the under surface to the summit of the cone. It is the
first formed and outermost layer of the cone and arises from the
most peripheral cells of the matrix plate ; it also comifies sooner
than any of the other layers of tlie hair. The inner sheaths and
tlie hair are formed later from the middle cells of the matrix plate.
Above the apex of the hair cone the cells arrange themselves to
form an axial column, which eventually comes into relation with

pepilla; (ll.-H., vitroDui Uyer; W„
i; T.-Dr.. aebafwous gland: W.-Sch.,
■ 230. (Afwr SWhr:

hair canal ceils abutting upon the superficial epidermis and indi-
cates the path along which the hair sheaths, and with them the hair,
must grow. The connective- tissue portions of the hair become more
distinct. The concavity on the under surface of the bulb becomes
filled by the large connective-tissue papilla, which consists of
abundant, transversely arranged cells and which as yet shows no
neck-like constriction. It seems to be covered by a very thin con-
tinuation of the vitreous layer and to be separated by this from
the epithelium. From the richly cellular connective tissue of the
hair follicle a denser homogeneous layer separates, especially in
the region of the swelling; this is the vitreous layer. The mus-

DEVELOPMENT OP THE INTEGUMENT. 269

cuhis arrector has at first the form of elongated cells, which show
the oblique course from the bulb to the epidermis that is char-
acteristic for the muscle; it becomes more distinct in this stage.

The follicle, gradually enlarging, grows obliquely downwards,
and all its constituent parts undergo further development until it
becomes the anlage of the actual hair. The sebaceous gland and
the swelling assume noticeable dimensions and the connective-
tissue papilla increases in height in correspondence with a deepen-
ing of the concavity of the matrix plate. While the bulb forces
its way downwards the cornified hair sheaths which arise from it
are pushed towards the surface.

As the last stage, that may be taken in which all constituents
of the hair are laid down (the sheath hair, Stohr). The hair
elongates, especially in that part which lies below tlie hair bed.
The upper part, with the swelling, sebaceous gland, and orifice,
grows somewhat with the further development, but in general
retains the same proportions. And, furthermore, it is the portion
of the hair follicle intervening between the surface of the skin and
the hair bed which remains unchanged throughout life, while the
processes connected with hair change and the subsequent death of
the hair take place only in the portions of the follicle below the
hair bed. The outer root sheath, except in its lowest portion, from
which the hair and its sheaths are developed, consists of two or
three layers of cells, the innermost of which is flattened agajnst the
inner root sheath and later is united with it (Stohr). The outer
layer consists of more or less high columnar cells, which, in
younger follicles, are all directed outwards and downwards (Fig.
209), probably in correspondence with the downwardly directed
growth pressure of the follicle; later they become arranged per-
pendicularly to the axis of the hair. Towards the completion of
development, when the hair change begins, the columnar cells be-
come very high and their nuclei round or hemispherical with the flat
surface directed outwards ; they lie in the inner portion of the cells,
while the outer portions, which rest upon the vitreous layer, are
clear and unstainable. On the outer surface of these high columnar
cells a homogeneous layer is secreted. The portions of this layer,
at first separated, fuse together to form the inner vitreous
lamella and unite intimately with the outer vitreous laver, which
is formed by the innermost layer of the connective-tissue portion
of the follicle. Later the two vitreous lamellae become closely
connected together. The columnar cells stand in small transverse
grooves of the vitreous layer, these grooves corresponding in width
with the cell bases and being readily recognizable in microscopic
sections, in which the vitreous layer is easily separated from the
follicle epithelium, as slight elevations between tlie rows of cylinder
cells. The vitreous layer terminates at the swelling, and above its

270 HUMAN EilBRYOLOGY.

,1 upper edge an especially

..-'"■"-— "^ strong layer of elastic

fibres lies close against
the epithelium and ex-
tends upward as far as
the sebaceous gland. In
H-i the swelling the epithe-

linm becomes many-lay-
ered, more so on the
anterior surface of the
follicle than on the pos-
'■' terior, which, from the

beginning, shows the
strongest development of
the swelling. At this
^^ point the arrector mus-
cle, surrounded from
below upwards with elas-
tic fibres, is usually in-
serted. Above the swell-
^ ing the epithelium again

, becomes thinner and its

"^ cells lower, and it is es-

peci al I y thin in the
region of the sebaceous
gland, at w h o s e orifice
the hair follicle has its
-a. smallest diameter (the
isthmus). At this point
"^' the funnel of the follicle
p. begins, not being formed
by a depression from
alx)ve, but by the eornifi-
cation, accompanied by
the formation of kerato-
hyalin, of the central
cells of the follicle and of
the h a i r - c a u a 1 cells,
whereby a long streak of
comified cells, which ex-
tends far into the epi-
dermis, is formed. This indicates the path which the hair will
shortly take, and, after it has broken tlirough, the funnel becomes
usually much widened and its walls strongly comified.

The lowermost part of the outer root sheath encloses the ele-
ments of growth for the hair. It has already been seen that in

Fio. 20B. — A compleW ly fo

isry region of oneiBht monlh

•n^efet

r. Partly sclismalic.

nan oblique HriH of

Hrtiiai., /'.p..ou.hionot«Bin

ue paiBllft; PJ:. nMk

papilla; /'.^., tip of papilla

jW.,h^i

matrix; GI.-H., viire-

[mm the outer root

r root :.he«th; Ubg..

Hineclive-liKBue portion of tol

cle: .S-.-D

., Bwdling; T.-Dt-.. wbaceo

a, ilancl:

Il.-Ka.. hair canal.

DEVELOPMENT OF THE INTEGUMENT. 271

younger stages Henle's sheath could be followed down to the
matrix and was the most external and at the same time the oldest
of all the structures which arise from the matrix. It also cornifies
the earliest and the most strongly of all the hair sheaths. Some-
where about the level of the connective-tissue papilla (according
to Gavazzeni, 1908, even in the matrix cells) there is formed in it
a ring of cells containing granules ; the nuclei of these cells do not
become smaller, as is nearly always the case in the stratum
granulosum, and their granules differ from keratohyalin in both
their chemical and staining reactions (staining with eosin and
fuchsin).

It would seem that these granules, as also those of Huxley's layer and of
the hair itself, are not keratohyalin, but a different chemical substance (trichohyalinf
Vomer, 1903). The granules of Henle's layer became converted into elongated
rods and soon disappear, the layer itself staining diffusely with eosin and becoming
completely comified.

Henle's layer covers all the central structures and extends to
the region of the hair canal, where it breaks up and is perforated
by the hair in its upward growth (Fig. 209).

Huxley's layer, the inner lamella of the inner root sheath,
cannot be followed quite down to the matrix plate, although it is
certain that it has its origin from a definite ring of matrix cells.
In the lanugo hair it extends at first far beyond the tip of the
connective-tissue papilla into the apparently undifferentiated mass
of cells at the base of the follicle, and in later stages of develop-
ment its trichohyalin-containing cells can be distinguished further
down toward the matrix. Its granule cells extend far upward
upon the shaft of the hair, which has formed in the meantime, and
they then become cornified. It stands in intimate connection with
the Henle layer, which has already become completely comified,
and between the cells of this layer those of Huxley's layer send
processes containing granules.

According to Garcia (1891) the sheaths can be followed quite
to the matrix plate in the head hairs of fetuses of eight to nine
months, when the hairs have just attained their complete develop-
ment. Of the forty to fifty cells which occur in a longitudinal
section through the summit of the matrix, Henle 's and Huxley's
layers correspond to four to six cells on either side. When the
hair, in its full strength, has broken through the inner root sheath,
this terminates in a sharp edge surrounding the hair in a circular
manner, at the level of flie isthmus below the orifice of the seba-
ceous gland ; at first it extends somewhat higher than this, as far
up as the hair canal.

Beginning somewhat higher than Huxley's layer, there are
formed from the more internal regions of the matrix the cuticle of
the inner root sheath (the sheath cuticle) externally and the hair

272 HUMAN EMBRYOLOGY.

cuticle internally. These two cuticles arise from the four to six
cell-rings of the matrix internal to those which form the inner root
sheath. Their cells contain no granules (whether they are also
destitute of granules in the adult condition is still uncertain), and
they comify probably before Huxley's layer, forming scales which
in the sheath cuticle are small and directed obliquely inwards and
downwards, while in the hair cuticle they are large and directed
obliquely outwards and upwards; in the fully developed follicle
the two sets of scales (imbrications) fit into one another. The
sheath cuticle is almost inseparable from Huxley's sheath, and the
hair cuticle, similarly, from the hair; and their imbrications ap-
parently determine the equal ascent of the hair and the hair fol-
licle, which their disappearance promptly disturbs (Von Ebner,
1876).

The hair itself arises from the large central portion of the
matrix plate. It forms at first an acute cone-shaped structure,
just as the sheaths do, and is covered by the comified sheaths as
with a cornucopia until it breaks through the torn sheaths in the
vicinity of the hair canal. Gradually it becomes broader, and
arises from the greater portion of the matrix. On the head (in
the eighth to ninth fetal month) each hair arises from twenty-
four to thirty of the cells seen in a greatest longitudinal section of
the matrix plate (Garcia, 1891), and Stohr's figures of the lanugo
hairs show about the same number. The large roundish nuclei
above the matrix gradually become elongated and the cells comify
without forming trichohyalin. The comification begins deep
down, the nuclei vanishing at the level of tlie junction of the lower
and middle tliirds of the follicle (head hairs, Garcia). Between
the matrix cells of the hair branched pigment cells appear, which
ascend into the hair and contribute pigment granules to its other
cells. According to the most recent views they take tlieir origin
from the epithelial rather than from the connective-tissue cells
(see p. 253). The diameter of the hair gradually diminishes as it
grows away from the papilla, and its smallest diameter is reached
with the completion of its comification. But before it becomes
hardened, the succulent hair mass is pressed, as in a mould, by
the elastic compression of the sheaths. Henle's sheath is a stiff
tube, which on account of its net-like structure (flat cells separated
by meshes, very well shown by Giinther, 1895, in his Fig. 202), may
exercise an elastic pressure. In it the soft hair with its soft
sheaths is compressed and moulded. The remaining sheaths form
a softer cushion for the forming tube. After the comification of
Huxlev's laver the hair with the cuticles and the inner root sheath
forms a compact cylinder, which is pushed upwards by new forma-
tion at the base of the follicle. The inner part of the outer root
sheath follows in the upward movement — ^the imbrications of the

DEVELOPMENT OP THE INTEGUMENT. 273

hair cuticle, firmly united to the hair, and those of the sheath
cuticle, firmly adherent to the hair sheath, seeming by their inter-
locking to determine the regularity of this upward growth.

The epithelial hair follicle is enclosed in a layer of connective
tissue, sharply marked off from the surrounding corium connec-
tive tissue, which is, in general, arranged horizontally. This con-
nective-tissue sheath consists of an outer layer of longitudinal
fibres and an inner transverse or circular layer. The inner layer
secretes the outer vitreous layer, whose connection with the colum-
nar cells of the follicle by means of the inner vitreous layer formed
by their bases has already been described. Beneath the hair bulb,
the papilla (papilla pili), which fills the spacious cavity of the
hollow hair bulb, projects from the connective tissue. It projects
from the mass of transversely arranged cells (the papilla cushion),
which lie below the entrance into the hair bulb, and extends some
distance upwards to form a papilla terminating above in a point
(the tip of the papilla). At the lower border of the hair bulb,
the papilla is constricted in a neck-like manner (papilla neck,
Garcia ) .

The cells of the papilla are partly directed obliquely upward
and partly are arranged transversely, as they are at their first
appearance. They are distinguished from all other connective-
tissue cells by their epithelial-like structure, being closely set cells
with large, roundish or elongated, darkly staining nuclei.

The first-formed hairs have only a short life.

Even before birth the first hair ehan^ begfins in the human species. This
is total, compressed into a brief space of time, and associated with a changre in
the quality of the hairs.

Some hairs cease to ^row even before they have broken througrh the surface
of the skin, a condition which is often shown in later life by lanupro hairs (such
as hairs of the face). In hair change the cessation of ^owth of the hair seems
to begin externally and to proceed internally. The cells of Henle's layer and then
those of Huxley's layer cease to proliferate and are carried upwards by the still
growing hair by means of the interlocking of the imbrications. Then the matrix,
the cuticles, and the hair itself cease their growth. The hair becomes cornified
right to its tip and, probably because it is no longer compressed by Henle's layer
at its lower end, this enlarges to form a brush-like structure, the hair being then
known as a bulb hair. A cell mass, the bulb cushion (Garcia), is formed by
the matrix and occupies the si)ace left vacant by the hair. This is carried out-
wards rapidly, as if squeezed out from the tube formed by the outer root-sheath.
The matrix and connective-tissue papilla pass outwards more slowly, and the
outer cells of the outer root sheath lose their columnar form (Aubertin, 1896, in
adult head hairs). A diminution seems to occur in the pressure which the growing
hair exerts downwardly and which is at first greater than that exercised by the
surrounding tissues; the pressure of the tissues is now alone active and the space
left vacant is filled by their being forced inwards.

During the ascent of the hair and its follicle the connective-tissue invest-
ments of the follicle thicken, especially the circular fibrous and the outer vitreous
layers. Perhaps these thickened layers exert a compression on the thinning lower

Vol. I.— 18

274 HUMAN EMBRYOLOGY.

part of the follicle, whereby the hair is forced outwards. But the thickening may
also be regarded as a protection against the pressure of the surrounding tissue,
or as the simple contraction of an overstretched membrane. Indeed, all mechanical
theories are to be advanced with great caution (Stohr), since in every step the
growth of the hairs apparently follows old inherited paths which, like the phylogeny
of the hair, are unfortunately poorly understood. All arrangements are naturally
intelligible mechanically and explicable as strain and pressure conditions; but
whether these mechanical explanations are correct is a question.

While the separated hair and the papilla are ascending the epithelial root
cylinder between the two becomes thinner; it becomes composed of cubical in-
diffei*ent cells and the connective-tissue papilla becomes smaller (diminishing at
the most to about half its original size in section). When the papilla has reached
its highest position, a new life begins in the root cylinder. It covers itself anew
from above with new columnar cells, becomes thicker, and develops a new swelling-
like outgrowth, which later applies itself to the old swelling (Garcia). Gradually
a new hair papilla forms in this, the hair matrix producing first a new inner
root sheath and then a new hair, just as on the first formation of the hair. As
the new hair grows out, its matrix and papilla are forced downwards by the
renewed growth, and the inner root sheath is broken through just below the orifice
of the sebaceous gland. The tip of the hair pushes its way, frequently in a
tortuous course, through the old follicle canal, and after a considerable enlarge-
ment of this the old hair, which projects considerably, eventually falls out, as
the result of some mechanical cause. The new hair is no simple replacement of
the old, but has a quite different character. W^hile the hairs of the first generation
are practically all alike, there begins to appear in the second generation the great
difference between the head and body hairs, and this increases in generation after
generation, until, at the beginning of puberty, the genital and axillary hairs begin
to differ from the lanugo of the remaining portions of the body; the lanugo of
the face gives place to the hairs of the beard, etc., in the male ; and the apparently
unaltered lanugo, as well as the head hairs, eyelashes, and eyebrows, assume a dif-
ferent type. In later years still more of the lanugo becomes transformed into
strong body hairs (terminal hairs, Friedenthal, 1898). Each change of hair
is at the same time a change in the chai-acter of the hair (type change, Unna,
1893). An accurate enumeration of the lanugo hairs on the human ear (Oshima,
1907) seems to show that the number of the fetal lanugo hairs is in places much
greater than that of the lanugo of the adult.

The direction of the hairs is determined from the beginning.
In the individual hairs it is recognizable in the hair-germ stage on
account of the bilateral form of the germ, and in later stages it
reveals itself by the hairs spreading out over the surface in the
manner permanently determined for them (Blaschko) and not
radially from some centres that arise. The same conditions have
already been described as occurring in the development of the
dermal ridges, which, in the same way, extend out over the surface
of the skin from the regions of their first formation (the finger
tips). With the completion of the hair formation the skin shows
an arrangement of the hairs which is definite, unchangeable in any
individual, and varying but slightly in different individuals, for
the knowledge of which we are indebted to Eschricht (1837) and
especially to Voigt (1857).

DEVELOPMENT OP THE INTEGUMENT. 275

The latter regarded the direction of the hairs as the result and an in-
dication of the mode of growth of the skin especially, but also, to a certain
extent, of the underlying portions of the body.. The general spiral arrangement
of the lines of the larger hair streams indicated a spiral growth of the enlarging
skin, such as is the rule in plants, a mode of growth which was thoroughly studied
by Ohlert (1854-55) and later by Schwendener (1909), and was regarded as a
peculiar law of growth for the animal body, the law of torsion, by Fischer (1880).
The centres of the spirals are the hair whorls, around which the hairs arise at
intervals and in curves which are regular even although they have not hitherto
been expressed mathematically. Voigt pointed out that the hairs at the ends of a
stream are further apart than they are near the whorl. A considerable number of
constantly occurring hair centres have the form of whorls, from which the hairs
diverge in spirals (the direction of the free hairs being towards the periphery,
diverging whorls). The more important of these are:

1. The crown or vertex whorl, curving towards the right in more than

half the cases, towards the left in about a third, and doubled in the
remaining cases (curving to the right on the left side and towards
the left on the right side), or, in rare cases, trebled.

2. A right and a left brow whorl.

3. A right and a left ear whorl.

4. A right and a left axillary whorl.

5. A right and a left lumbar whorl.

6. Occasionally one or frequently two whorls, right and left at the side

of the body (often only on one side).

7. Hand and foot whorls.

In other regions the hairs converge from all directions to form converging
whorls, the most constant of which are:

1. The frontal whorl, at the root of the nose or at the edge of the scalp^

or in both places.

2. Lateral cervical whorls.

3. Elbow whorls.

4. Umbilical whorl.

5. Penial whorl.

6. Coccygeal whorl.

The hair lines meet one another at acute angles in streams; when they meet
at right angles crosses are formed, such as the nasal cross, the hyoid cross, the
pectoral cross, the abdominal cross, the penis cross, and the coccygeal cross in the
middle line of the body; the brow crosses, the nape crosses, the supra-auricular
crosses, and the lateral crosses, one on each side; and the shoulder crosses, the
ulnar crosses, the carpal crosses, and the crural crosses on the extremities. Many
are doubled, and very frequently one is absent on one side of the body.

The diverging whorls, according to Voigt, are regions of least growth, of
comparative rest; the converging whorls correspond to especially gi'eat stretching
of the skin, in regions where (either in the ontogeny or phylogeny) some organ
projected from the body (Wiedersheim: penis, umbilicus, branchial clefts, and, in
animals, horns), or where especially strong growth resulted from the pressure of
adjacent parts (coccyx, elbow). The crosses are regions of relative rest, lying
between forces acting from either side; the converging hair streams are regions
which became stretched during growth.

Of the arrangement of the hairs in transverse rows, corresponding to the
arrangement of the scutes in transverse girdles around the body and limbs of
reptiles, and of the development of such rows, we have as yet no comprehensive
investigation.

276 HUMAN EMBRYOLOGY.

G. THE SUDORIPAROUS GLANDS.

The development of the sudoriparous glands begins on the
finger tips (Blaschko, 1888), the palms of the hands, and soles of
the feet (Grefberg, 1883) in the fourth month; according to
Kolliker (1889) in the fifth month. It follows immediately upon the
formation of t|ie dermal ridges. Their anlagen resemble closely
those of the hairs, except that they lack the close aggregations of
cells in the corium, from which, in the case of the hairs, the papillae
are formed. The anlagen project downwards as solid flask-shaped
rete papillae, which, becoming long and slender, begin to become
tortuous in the sixth month. In the seventh month a lumen begins
to form in each, the beginning secretion producing intercellular
clefts which later unite to form a continuous cavity. In the mean-
time the lower end, bending upon itself, forms the anlage of the
coiled portion of the gland. The outer terminal portion of each
gland forms its own lumen, which later unites with that of the
glandular portion. The two-layered epithelium of the duct portion
becomes transformed at its passage into the glandular portion into
two distinct layers; the inner of these remains the large-celled
secretory layer, while the outer becomes flattened and forms the
epithelial muscular layer (Kolliker, 1889). The gland canal is
then composed of an inner layer of cubical, or even higher,
glandular cells, with large, round nuclei, and of an outer layer of
flat muscle cells, whose nuclei are flattened and whose angles pro-
ject between the cells of the inner layer; these cells form an outer
investment of closely set parallel striae around the gland. At the
time of birth the sudoriparous glands, like the hairs, seem to be
completely laid down, so far as their number is concerned.

In the hairless palms of the hands and soles of the feet it is
certain that the sudoriparous glands arise from the surface epi-
dermis, and in most of the other portions of the skin they seem
to have a similar origin in man. In many places, however, a rela-
tion of the sudoriparous glands to the hfiir follicles, of general
occurrence in animals, persists, the sudoriparous glands partly
developing directly from the uppermost portions of the hair fol-
licles (Wimpfheimer, 1907; Diem, 1907), or partly having at
least a connection with its follicles at their mouths (Fig. 209).

The idea that the follicles and the sudoriparous glands belong to genetically
single areas has been somewhat generally accepted; according to my observations
the hair disks (not constant in their occurrence) also belong to these areas, each
of which, with all its appendages (vessels, nerves, muscles) corresponds in its
original form to a promammalian scute (scute area or hair area). According to
this view the completely isolated sudoriparous glands of the palms and soles
must each represent the remains of a hair area (Whipple). That in spite of an
imperfect development of the hairs the sudoriparous glands may actually retain their
proper places in the hair areas, I have been able to show in the sole of the foot of

DEVELOPMENT OP THE INTEGUMENT. 277

Omithorhynchua (Pinkus, 1905) where the paradosical arrangement of a romples
consisting of a sudoriparous gland behind, a simple hair follicle in the middle,
and a hair disk anteriorly, can only be explained as a semicircular arrangement n£
the elements of the hair area, peculiar to Ornithorkynchus, and a disappearance of
all the hairs with the exception of the middle one. A further small step in the
reduction wonld leave nothing remaining but the sudoriparous gland. The con-
nection of the sudoriparous gland with the hair follicle, regarded as merely a
topographical relation by Maurer (1895), but by most authors (De Meijere, 1894;
Eggeling, 1904) as genetic, has been demonstrated to be of the latter nature by the
embr>-o1c^cal obsenations of Stohr's pupils, Wimpfheimer and Diem, who found
that in the majority of the mammals examined the sudoriparous glands arise from
the follicle epithelium and their orifices only later migrate to the surface epidermis.
Usually the sudoriparous gland is fonned,
like the other appendages of the hair
(sebaceous gland, swelling, muscle, hair
disk), on its posterior surface. It begins
to form even in the hair germ stage and ^
becomes distinct in the papilla stage
(although not visible in man). Its cell
nuclei, in contrast to those of the col-
umnar layer of the hair, are small ^
(Eggeling); in contrast to the regular
arrangemeut in the anlagen of the seba-
ceous glands they are irregular (in the
mole) ; and the increase in the number of
the connective- tissue cells, which usually
begins early in the case of the hair germ,
is wanting beneath them. Unfortunately,
in man, as well as in many other mammals,
the original mode of development of the
sudoriparous glands cannot be obsen-ed.
In these forms they appear to arise, for
the most part, not from the follicle Fio

epithelium, but from the surface epidermis. %*Dr'

not extend quite cl«r1y «»iu«h to the (luici):

r)onn rtiirdti frnm tllP liminl S.-Dr., (udoriparous gland: H.-Ka., hair canal.

UepariUreS irom me USUaj ^ j^ AtWrStObr, trom Diem: Entwicklunj

structure of the sudoriparous der8ch™»-drUMiianderbeli»»r««iHautder

, , . , . ■ n SiuBetiem. Fig. 7.

glands occur in certain regions oi

the body. If we make exception of the eyelids with their specialized
glands, these regions are the mammary and axillary regions,
the inguinal folds with the scrotum, and the anus. In some cases
the characteristic peculiarities are recognizable in the anlagen
(region of the mammary gland), in others they first appear at
puberty (the axillary glands).

A. The Glands of the Mammary Begion. — The ventrolateral
surfaces of the embryo at an early stage (6.25-6.75 mm., Keibel
and Elze, 1908, "Normentafel," Nos. 21, 24, and 25, Figs. 11 and
12) are occupied by a broad diffuse area of high epithelium
{Schtcalbe's milk streak), that has a variable development, ex-
tending in some cases forward over the branchial arches and back-
wards, over the limb buds, until it reaches the tail; but in other
cases it is of less extent and may be completely wanting. This

278 HUMAN EMBRYOLOGY.

epithelial tbickening rei)re8ents a formative region, which occurs
also in the lower raammals and in birds (Heinrich Schmitt, 1898).
In it, especially in its anterior portion, there develops in embryos
9 mm. in their greatest
hngth (" Normentafel,"
Nos. 37-39) the milk line
or milk ridge (O. Schultze,
1892), a band of thickened
epitlielium which is ap-
^ proximately lenticular in
transverse section. The
milk ridge is a structure
comparable to the gan-
glionic or dental ridges,
glandular anlagen appear-
ing in it from place to
place (O. Schultze, 1897;
Broulia, 1905). In it the
anlage of the mammary
gland develops in man.
Its primary epithelial an-
lage is, according to Rein ( 1882) , (a) mound-8hai)ed, consisting of an
aggregation of epithelial cells projecting beyond the surface of the
epidermis. Even in embryos with a greatest length of 9.5 mm. it

has become (b) fliitty lenticular, projecting somewhat beyond the
epithelium both above and below, and being surrounded by an
aggregation of corium cells {nipple zone). As the result of strong
downward growth there is formed (c) the papilla-shaped anlage
{Fig. 211), from which (rf) the hulb-shaped anlage is formed as

DEVELOPMENT OP THE INTEGUMENT. 279

the lower parts increase in breadth while the more superficial por-
tion becomes constricted in a neck-like manner. Later the milk
ducts begin to sprout out, the anlage becoming polygonal and beset
with short buds, {e) the period of bud formation. The develop-
ment progresses slowly. Several simple papillae project down-
wards into the connective tissue from the epithelial mass, and in
the eighth month these become hollow and somewhat branched,
their terminal portions being large (Fig. 212). The primary epi-
thelial bulb from which these milk ducts arise becomes cornified in
its central portion and a cavity forms in it, with which the lumina
of the gland ducts become continuous (Fig. 212). When the hair
development begins the region around the mammilla becomes
conspicuous, on account of the absence of hairs on its surface,
and forms the nipple area (0. Schultze, 1897).

In addition to the paired mammae, supernumerary mammary
glands are frequently developed. As a rule, they occur along
a line from the anterior axillary fold to the inguinal region and
make it seem as if several mammary glands had formed from the
milk ridge; in other cases the hyi>erthelial structures are arranged
irregularly in the mammary region.

The anlage of the mammary gland is usually compared with those of the
sudoriparous glands. In the monotremes the glands of the mammary pouches
in their functional condition differ from the ordinary sudoriparous glands only
in their exceptional size (Gegenbaur, 1886, who, however, originally derived the
mammary glands from sebaceous glands). Their genetic origin from sudoriparous
glands is shown both by their development and by their comparative anatomy.
Futhermore, in the adult condition tlteir hidradenoid structure, represented
by the two-layered epithelium of the ducts and the simple epithelium in the
glandular alveoli, is an indication of their sudoriparous character. Their
glandular alveoli, like those of the sudoriparous glands, produce their secretion
without destruction of the cells (Bertkau, 1907) and are enclosed within a
muscular network (Benda, 1893), which resembles the basket-like muscular net-
work of the sudoriparous glands in the snout of many animals (Kormann, 1906).
Their similarity to sudoriparous glands is rendered still greater by the fact that
such glands, modified along the lines of the mammaiy glands, are formed in the
neighborhood of these structures. Rein (1882) has already identified these as
the anlage of the Montgomery's glands. Close around the nipple a number of
sudoriparous glands is fonned from a primary epithelial anlage similar to that
of the mammary gland itself, but smaller; they resemble milk ducts by possessing
peculiar outpouchings and wide lumina. Occasionally sebaceous glands and small
hair anlagen are to be seen arising from the same epithelial papillae, so that the
hair areas, whose remains are represented by the accessory mammary glands
(Eggeling, 1904), are in these cases not absolutely rudimentary (Brouha, 1905).

In rather early stages (embrj'os of 15.5 mm., Walter, 1902) some other
epithelial appendages begin to develop around the mammary glands and were at
first regarded as hyperthelial structures (accessory mammary glands, Hugo Schmidt,
1896). From another standpoint they were interpreted as marsupial anlagen
(Walter), similar to the marsupial pouches which fonn around each mammary
orifice in the opossimi and fuse by their outer ends on the appearance of the
marsupium (Bresslau, 1902). The number of these anlagen is occasionally very

280 HUMAN EMERYOLO0Y.

large in human embryo^ reaching in some cases forty; tliey are scattered around
the nipple and ai^ far up as the axilla, and are nsitatly smaller than the milk
glands proper. Up to the pi'esent they have not been found in fetuses longer
than GO mm. To the same category perhaps belongs also the inguinal epidermal
aniage, which has been described by Brugsch and Unger (1903).

In the same situation as these epithelial thickenings I have found around
the mammary gland during my preparation for Ihe present work, in a fetus
of 85 mm., five epithelial structures, which must be regarded as something quite
distinct. They are long tubules, surrounded by a thin longitudinal layer of con-
nective tissue and formed of a two- to four-layered epithelium, which bounds a
small lumen, not opening to the surface. Near the epidermis the most superficial

FlQ. 213.— Epitbeluil BppepdsEe owumng nrar thf nummaol the frtug from which Fig, 211 wuUksD.
H., comifibl plug with kentohyalin: L.. lumen: M.. DUBCle (T). A 180.

portion of the tubule contains a small cavity, filled with eomified cells and sur-
rounded by keratohyalin cells; it resembles Stiihr's hair canal, and neither opens
to the exterior nor communicates with the lumen of the tubule. Below, the
tubule, beyond the termination of its lumen, ends in an epitheliol thickening, which
sometimes forms a very regular, almorf conical structure, covered e.-iternally by
columnar cells (Fig. 2131. These epithelial tubules are, with the exception of the
mamma, the tai^i^Ht epithelial appendages of the fetus. At this stage the bair
aniagen are .still in the stage of the much shorter bulb papilla and the sudoriparous
glands are not yet formed. I would assign the tubules without question to the
mammaiy apparatus, were it not that similar, longer structures occurred in the
nasal mucous membrane (Fig. 214). Possibly those in the pectoral region are
a form of the further development of the epithelial structures of Schmidt (1896),
mentioned above; probably they are forerunners or early stages of the Montgomery
glands of the nipple area. That they are glands of the sudoriparous system is
shown by their complete similarity to the ciliarj' sudoriparous glands, Moll's

DEVELOPMENT OF THE INTEGUMENT. 281

glands, whose development from the epithelium of the hair follicles and occasional
occurrence qiute separated from these has been described by Ask (1908). The
ciliary glands are, at this stage, howei'er, younger, and only in fetuses of 170-250
mm. show the grade of development in these structures seen in So mm. fctuseii.
On the same side of the ciliary follicle as the sebaceous gland and swelling (the
outer surface of the eyelid, but the posterior surface of the cilia) there extends
above the level of the sebaceous gland a thin elongated epithelial cord, vhichr
after passing over the sebac«ous gland, bends downwards and is continued down-
wards for some distance parallel to the aniage of the cilium, to terminate in a
pear-shaped enlargement composed of small rounded epithelial cells. Later a
lumen appears at the orilice and another in the coiled portion of the gland. The-
connective-tissue cells around the aniagen of Moll's glands are not, however, in-
creased in number.

Fio. 2M.— AnmilaTBirithclisi ttruclurelromihvDual cavity of the nunc tufa. X 180.

B. The furtlier development of the axillary glands begins in
the ninth year in the female, but not until the time of puberty in
the male (Liineberg, 1902). They are formed from the ordinaiy
sudoriparous glands of this region, a large number of which per-
sist as small glands. The large axillary glands form a continuous
layer of large, partly branched tubules, with an inner layer of high
secreting cells and an outer single-layered muscle coat.

Nothing special is known concerning the development of the
inguinal and scrotal glands.

H. THE NAILS.
At a very early period the place where the nail will be formed
is recognizable on the dorsum of a terminal phalanx. The
primary nail field (Kolliker, 1888), primary nail base (Zander,

282 HUMAN EMBRYOLOGY.

1884), is recognizable in microscopic sections in fetuses of 4.5 cm.,
while in those of 2.75 cm. the region in which it will develop is quite
undifferentiated (Okamura, 1900). Externally, the primary nail
field somewhat later becomes evident on account of its smooth
appearance and its firmer adherence to the subjacent tissue, as
well as by its sharp anterior, posterior, and lateral boundaries.
It extends from the finger tip almost to the articular process of the
terminal phalanx — an extent which the fully formed nail also pos-
sesses and which is only relatively diminished transitorily during
development by the increased growth of the ball of the finger. At
its proximal (posterior) edge the epidermis invaginates to form
a transverse, posteriorly convex pouch (the root lamella of
Kolliker, the posterior nail fold of the adult), in which later the
nail matrix is formed and whose roof is termed tlie nail wall.
The epithelial invagination is the posterior limiting furrow (Kol-
liker), and laterally, on each side, it is continued into a lateral
groove (the lateral nail fold, bounded externally by the lateral nail
wall). Anteriorly the primary nail field abuts upon a shallower
depression, which bounds it anteriorly in a transversely arched
manner (the anterior groove, Unna; nail fringe, Kolliker). The
primary nail field is flatly convex and is at first distinguished from
the two- to three-layered skin of the fingers by its three- to four-
layered epithelium with a germinal layer of cubical cells. Later
on, also, the cells of the lowest layer of the nail field (the later
nail bed) remain cubical, in contrast to the columnar cells of the
nail fringe, the nail fold, and the germinal layer of the rest of the
epidermis of the finger. In front of the nail fringe a transverse
ridge appears, which is of great importance from the comparative
standpoint. It corresponds to the region of the skin in which later
the looser cornification, seen under the free edge of the nail and
equivalent to the sole plate of the other mammals, is formed
(Boas, 1894). In front of this ridge the epidermis is depressed
to form a groove (the distal limiting furrow, Kolliker). The
germinal layer in this region is formed of high columnar cells and
the epithelium is five- to six-layered. In front of the sole plate
the germinal layer becomes still more columnar.

The periderm and the stratum intermedium extend over the
entire anlage, levelling its surface. The most superficial layer of
very flat cells desquamates to a remarkable degree; and one finds,
still adhering to the surface, cells swollen to a vesicular form and
with small pyknotic, darkly staining nuclei (for a description of
these cells see especially Zander, 1884; Kolliker, vesicular cells;
Okamura; for those of the chick embryo, Rosenstadt, 1897).

In the course of further development the region of the sole
plate becomes higher and eight- to ten-layered, and the cells of the
nail field become flat, so that by its cell form alone the dorsal sur-

DEVELOPMENT OP THE INTEGUMENT. 283

face of the terminal phalanx oan be readily distinguished from the
volar surface, the germinal layer of which remains columnar.
Only in the neighborhood of the nail wall, and, later, still further
proximally also large vesicular, round cells persist at the surface,
to a greater extent on the toes than on the fingers. The flat peri-

Fio. 31G. — Msdiu longiludinAl Bection ttiroueh <he index finger of a humui feliu of 8,5 cm. N.-F^
n»U fold; H.-W.. nail iniU: pr. Or.-F.. proximal limiting Itinow: Ke.. keratohyalin liiye^ jV,-S,. naU

derm cells, beginning at the nail fringe, fuse to form a tough super-
ficial layer, and between them and the cubical germinal layer
there lie distally several layers of prickle cells and proximally,
at the nail fold, an area of pale vesicular cells (Zander's limit-
ing layer). These vesicular cells
remain large until much later on
the toes, but on the fingers they
become flatter, i)robably in cor-
respondence ^itli the greater ^r.
general flattening of the anlagen
of the finger nails.

Below Zander's limiting
layer there is formed from the j_

uppermost portions of the stra-
tum intermedium, in somewhat F„.2,e._Tr.„„,««,tion .h™nghthe.-r.

larger embrVOS (10 cm., Zander; mlnal pholanxot another finger of the tame fetus
nn TJ---I1-1 a K from which Fig. 2lfi i» taken. The bssal osll layer

9.3 cm., Kolllker; 8.5 era., aC- i,cubimldor«lly. columnar voUnv. .V.F.,lateral

cording to my own ohserva- ^j/'^i*'^'' '"""«*■>•'''' '">''^ '"-«- «"""''
tions), a stout layer with abun-
dant keratohyalin gramdes, which are partly large and roundish
and partly quite fine and dust-like. Beneath this granule layer,
whose keratohyalin nature was first determined by Pollitzer
(1889), there lies a layer of pale vesicular cells, which also, espec-
ially at the cell peripheries, contain granules similar to those of the
superjacent layer. These three layers form Unna's eponychium
<1883), and the nail itself is formed from them according to

284 HUMAN EMBRYOLOGY.

Kolliker, while according to Zander it is formed from the limiting
layer, which is continually reinforced from the subjacent kerato-
hyalin layers. The eponychium with its granule layer represents,
according to Zander, only a precocious comification, of the same
type as that which occurs in the epidermis over the whole body
at a later stage, when the granule layer, at the first sign of comifi-
cation, forms from the layer of prickle cells. This kind of comifi-
cation is found in such early fetal stages not only in the nail anla-
gen, but in all places where large appendage structures of the skin
are being formed. It occurs also at the openings of the peculiar
long epithelial appendages to be found in the nasal mucous mem-
brane and around the mammary glands, and it occurs in slightly
later stages in the development of the hairs, in the anlagen of the
hair canals. It appears to be merely an indication of increased
formative force in the epidermis. This layer of actual comifica-
tion, already similar to the later comification, cannot, however,
be directly identified with the periderm (eponychium). This is an
actual horn layer, which remains partly retained throughout the
rest of life (as the fringe at the proximal edge of the nail; see
below). Okamura (1900) is correct when he regards as the peri-
derm merely the outermost layer of desquamating cells, which lies
over the keratohyaJin layer, for we have already seen, in the
consideration of tlie general skin, that the periderm in man is not
a special layer, but merely the outermost layer of the quite young
epidermis, which in the later development of the skin is perma-
nently cast off.

The nail itself is formed from the region of the nail fold, quite
without keratohyalin formation, in the manner described by Unna
(1883) and confirmed by Okamura (1900) and Apolant (1901).
The actual nail formation begins at the posterior part of the nail
field, under the eponychium, as a layer of cornified cells. It begins
in the fifth month (Unna), in fetuses 17 cm. in length, the first
indications of its cells being visible in those of 16 cm. (Okamura.
1900). These cells lie at the entrance of the nail fold, at the level
of the distal end of the nail wall. They present fine granulations,
which do not take the stains which color keratohyalin, but stain
with picric acid, swell in strong alkali, and are insoluble in all
ordinary reagents such as water, alcohol, xylol, chloroform,
ammonia, acetic, hydrochloric, and nitric acid, alkalies, and
digestive ferments ; therefore they cannot be keratohyalin. They
have been termed by Ranvier onychogenons substance; but they
neither represent a special substance (onychin), nor are they really
granules, but probably nothing but the cross sections of
fibrillae. They consist of keratin and are the cross sections of
keratin fibrils which occur in the nail cells (Unna, Apolant).

The comification takes place, without being accompanied with

DEVELOPMENT OF THE INTEGUMENT. 285

a formation of keratohyalin, in the cells of the nail matrix, which
extends from the posterior (proximal) margin of the fold to the
anterior (distal) border of the lunula. The cells flatten and be-
come converted into platelets, which, compose the solid substance
of the nail. The formative region for this reaches, with advancing
development, from the original point to the deepest part of tlie
posterior nail fold, and anteriorly to the anterior border of the
lunula. Over this area the nail is formed and pushed forward

Fio. 217.— LangitudiDal Krtina throuch ths ksntohyslin l&ysr of the fetal Dsil bed, ulterior port. From
a human fetus of 8.5 cm. (see Fig. 215). X 380.

from the beginning, just as it is throughout the whole of later
life. The newly formed nails are for some time completely covered
by eponychium, hut later tins is thrown off and the surface of the
nail is exposed. Nevertheless a portion of the eponychium per-
sists throughout life as a small membrane resting upon the proxi-
mal end of the nail; this grows forward with the nail and sooner
or later desquamates at a distance of from 1-3 mm. from the pos-
terior nail wall. The anterior edge of the nail is at first very thin

Fia. 218 —Transverse serlion through the keratflhyalin layer of the nail bed, posterior part. From a
bumaafetusofS.Scm. (seeFiB.2l{i). X3S0.

and projects in older fetuses and after birth at the anterior end
of the phalanx as a delicate membrane, but it is verj- quickly re-
moved by the accidents of extra-uterine life (washing, movements)
(Unna). The nail then grow-s, becoming gradually stronger,
throughout the rest of life continuously, unless interrupted by some
pathlogieal condition. The portion of the skin on which the nail
rests in front of the lunula takes no part whatever in the forma-
tion. Its rete papilla, wliich form at the same time as the rete
papillse and ridges of other regions, produce the longitudinal
ridges of the nail.

286 HUMAN EMBRYOLOGY.

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u. pathol. Anat., vol. iv, 1893.
ScHREiBER, L., and Schneider, P. : Eine Methode zur Darstellung von Pigmenten

und ihren farblosen Vorstufen, mit besonderer Beriicksichtigung des Augen^

und Hautpigments, Miinchen. med. Wochenschr., No. 37, 1908, p. 1918.
Schridde: Die Protoplasmafasern der menschlichen Epidermiszellen, Arch. f.

mikr. Anat., vol. Ixvii, 1906, p. 291.
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vol. viii, 1892.
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Berlin, 1896, p. 87.
Grundriss der Entwicklungsgeschichte des Menschen und der Saugetiere,

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Schwendener: Vorlesungen iiber mechanische Probleme der Botanik, bearbeitete

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Verhandl. Anat. Gesellsch., Rostock, 1906, p. 209.
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Anat. Gesellsch., Heidelberg, 1901, p. 26.
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DEVELOPMENT OP THE INTEGUMENT. 291

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XL

DEVELOPMENT OF THE SKELETON AND OF THE

CONNECTIVE TISSUES.

By CHARLES R. BARDEEN, Madison, Wis.

GENERAL FEATURES.

In the bodies of most living things certain tissues are differ-
entiated for the purpose of passively supporting or protecting the
physiologically more active structures. These tissues are charac-
terized in the higher vertebrates by the predominant amount of
•extracellular substance, usually fibrous in nature, which, in large
part at least, is differentiated during embryonic development
from the peripheral portions of branched anastomosing cells.
According to the nature of the intercellular substance the support-
ing tissues are subdivided into white fibrous and yellow elastic
tissues, reticulum, cartilage, and bone.

In early embryonic stages the branched anastomosing cells
which compose the supporting tissue or mesenchyme, form an
extensive continuous framework. Certain parts of this framework
are differentiated into the definitive skeleton and other parts into
connective-tissue structures which protect and support the paren-
chyme of the various organs of the body and attach these organs to
the skeleton.

The development of the various connective-tissue structures
may be considered from two aspects, that of histogenesis and that
of organogenesis. The histogenesis of the connective tissues has
been most carefully studied in the lower vertebrates, in which the
cells are large and the conditions are relatively simple. Organo-
genesis has been more carefully studied in man than in any of the
lower forms. The histogenesis pf the connective tissues is appar-
ently similar in the different vertebrates. Study of the histogene-
sis of these tissues in man and the higher mammals in general
serves to confirm the results found in the lower vertebrates. Or-
ganogenesis is peculiar for each species, although there are funda-
mental similarities to be observed in related forms.

We shall first give a brief account of the histogenesis of
the connective tissues with especial reference to man and then treat
with more detail the morphogenesis of the human skeleton. The
specific development of the intrinsic supporting connective-tissue

292

HISTOGENESIS OF THE CONNECTIVE TISSUES. 293

framework of the various organs is most conveniently taken up
in connection with each of these organs, and will therefore not be
attempted liere.

PART I.

Histogenesis of the Connective Tissues.

(a) Early Mesodermic Syncytium.

In the youngest human embryos which have been described
there is present a well-developed layer of tissue composed of
branched anastomosing cells. This tissue layer surrounds the
amniotic and yolk-sacs and lines the chorionic vesicle (Fig. 219, A).
It forms a continuous sheet between tlie epithelium lining the

Kp.

Fio. 219. — Dia«r«mmatic pectionn tlirough two young human embo-os dncribei) by Oral Bpee.
A. IV. Sp«. ArFh. f. Anat. u. Fliysiol., Anal. Abt., 1S96. Taf. I. Fig. 3.1 llalf-acheniBtic xagiiul B«lJon
thruugh Graf Spec's embryo v. H. B. (Kbcnda. Ts(. I. Fig. I.) [laLf-xchematio sugittiJ necuon (hrough
Gnf [jpee-s embryo die. C. <Ebenda. 1SB9, Taf. XI, Fig. 14.) Tmnsvene i<ectioa through (he eDibo'onic

C chorda aniage; f^,. chorion; en., caoalii neurentericus; cf., yolk^E
p, blood ialBads; h., lieert; kp,, region o( primitive etrcak; M.,

amniotic cavity and that lining the yolk sac. The origin of the
tissue is imeertain. It evidently is homologous with tlie mesoderm
which in many of the mammals is known to arise from the primitive
streak and head process.

In man the primitive mesoderm is apparently formed before
the appearance of the medullary plate, the neurenteric canal, and

294 HUMAN EMBRYOLOGY.

the primitive streak. After these structures appear the mesoderm
disappears in the mid-axial line anterior to the primitive streak,
and a chordal plate is differentiated in the entoderm. (See Fig.
219.)

(b) Formation of the Mesodermic Somites.

In Graf Spee's embryo Gle (Fig. 219, B and C) the mesoderm
extends on each side of the neurenteric canal and of the medullary
groove (Fig. 219, C) to the anterior extremity of the embryonic
anlage where the mesodermic sheets of both sides become united
(Fig. 219, B, h). Posterior to the neurenteric canal the mesoderm
is intimately united to the tissue of the primitive streak, a region
of active production of mesenchymal tissue. At the outer margin
of the embryonic anlage the mesoderm is continuous posteriorly
with the mesenchymal lining of the chorion, laterally and ante-
riorly with the mesodermic covering of the yolk sac and amnion
(Fig. 219, B and C).

At a slightly later period the sheet of mesoderm on each side
of the neural tube becomes longitudinally separated from the more
laterally situated mesoderm (Fig. 220, A and C) and at the same
time divided into a series of segments (mesoblastic somites). In
the chick the first somites formed are the occipital somites (J. T.
Patterson, Biological Bulletin, 1907, vol. xiii, p. 121), then follow
in turn the cervical, thoracic, lumbar, sacral, and coccygeal. It is
probable that the first somites formed in the human embryo belong
to the occipital region. In the latter half of the first month of
development in the human embryo there are found anterior to the
cersdcal myotomes three incomplete occipital myotomes. The rela-
tions of these myotomes to the first somites differentiated have
not yet been definitely determined. Etemod (Anat. Anz., 1899,
p. 131) has described an embryo with eight somites, Kollmann
(Anat. Anz., 1890, Arch. f. Anat. u. Physiol., Anat. Abt., 1891)
one with fourteen (Fig. 220, A), and Mall (Journ. Morphol., 1897)
likewise one with fourteen. Mall considers the first three somites
in his embryo to be occipital somites. They probably correspond
with the first three somites in the embryo described by Kollmann
and possibly with the first three in the embryo described by
Eternod.

The occipital somites are probably not completely divided oflf
either from one another or from the lateral mesoderm (Figs.
229, 230, A).* The cervical somites, at least the more distal ones,
on the other hand, become completely separated, and the tissue in

' Kollman states that in his embryo Biille, with fourteen somites, the segmen-
tation externally appears well marked in the post-otic re^rion, but intemally^ is
apparently incomplete. (Pei'sonal communication to the author.)

HISTOGENESIS OF THE CONNECTIVE TISSUES. 295

" M«luU&ry tubs

't.

Fic. 220.— A. [After Kollm»nr
Human embryo with fourU«a Homitt
section througli the region behind t^
Arch, f. Anat. u, Phy><ii>1.. Anst. Abt.
o( MmiteB ot the embryo Bhowu in F.

", 2.5 mm. long. Mogn.
1891. Piste III, Fit. 3.1

ituogiienihichte des Mensthen, Fis. It9.)
30 t I. B. (Ebnula, Fig. 5S.) Transvene
lOWQ in Fig. 220. A. C. (After Kollmann.
Tiwuvene MCtion (hroujh the tenlh pair

296 HUMAN EMBRYOLOGY.

each assumes an epithelial character and becomes arranged about
a central cavity or myocoel (Fig. 230, d). At the posterior end of
the cervical region a solid column of cells marks for a short period
the remains of the neurenteric canal. Bevond this in the axial
region lies the tissue of the primitive streak which is continued
into the mesenchyme of the allantoic stalk. In subsequent develop-
ment mesoderm is differentiated from the anterior end of the
primitive streak on each side of the posterior end of the neural
groove. In this mesoderm successive somites are formed. Finally,
as the differentiation of the body extends posteriorly, a definite
primitive streak gradually gives way to a mass of mesenchymal
cells situated between the ectoderm and entoderm, and then, in
the caudal process, to a mass of cells entirely surrounded by ecto-
derm. From this mass of cells are successively differentiated the
more caudal mesodermic somites.

(c) Axial Mesenchyme.

As the chorda dorsalis becomes differentiated (see below)
marked changes take place in the somites. For a time these consist
of epithelial tissue which surrounds a central cavity or myocoel
(Fig. 220, C). Toward the end of the third week the cervical and
thoracic myocoeles become gradually filled with branched spindle-
shaped mesenchyme cells which come from the surrounding epithe-
lium. The medial wall of the somite opens, and the mesenchyme
cells wander out toward the neural tube and the chorda, and give
rise to a tissue which ensheathes these organs (Fig. 221). The
mass of mesenchyme derived from each somite represents a sclero-
tome. The successive sclerotomes soon fuse so as to give rise to
a continuous mass of mesenchyme. The mesenchyme of the two
sides becomes fused. Alter gi\'ing rise to the sclerotomes the
somites become converted into myotomes, the further fate of which
is described in the section on the development of the muscular
system. In many of the lower vertebrates the lateral layer of
the myotomes gives rise to dermis, but in mammals the dermis
comes chiefly, if not wholly, from axial mesenchjTne. (Bardeen,
Johns Hopkins Hospital Eeports, vol. ix, 1900.)

(d) Parietal and Visceral Layers of the Mesoderm.

During the formation of the embryonic coelom, the lateral
tmsegmented mesoderm plates become divided into two layers, a
parietal layer and a visceral layer (Figs. 220, C, and 221). The
cells facing the coelom assume an epithelial character. The deep
strata of the parietal layer give rise to scleroblastema, from which
some of the skeletal apparatus and connective tissues of the trunk

HISTOGENESIS OF THE CONNECTIVE TISSUES. 297

and limbs are derived. The deeper strata of tlie visceral layer
give rise to the connective tissues as well as to the musculature of
the thoracic and abdominal viscera.

(e) Meseochyme of the Head.
The axial mesoderm of the trunk is continued forward on
each side of the chorda dorsalia to the region of the base of the
midbrain. From it arises a large part of the mesenchyme of the
head, including most of that which gives rise to the skeletal struc-
tures of the cranium and the upper part of the face. The trans-
formation of mesoderm into definitive skeletal structures is more
direct in the cranial than in the spinal region. The formation of
somites for the axial region of the head is restricted to the postotlc
region, and even here it is, as mentioned above, less complete than

Flo. 221.— (AftiT Kollnmnn, Arch. f. AnM, 0. Pni-jiol.. Anal. Abt.. 1891, Plata III. FL(. 8.) Tran-veres

in the trunk. The cranial mesoderm apparently is largely con-
verted into mesenchyme without going through that process of
division into somites characteristic of the spinal mesoderm. The
mesenchyme near the chorda in the occipital region shows no
segmentation in the latter half of the first month. More laterally
segmentation is indicated by the formation of myotomes from the
dorso-lateral portion of the mesoderm. Near the myosepta the
mesoderm may show a slight condensation.

In the prechordal mesenchj-me of the head there are differ-
entiated in many vertebrates vesicular cavities, "head cavities,"

298 HUMAN EMBRYOLOGY.

lined by epithelium, from which musculature and mesenchyme
arise. There are four such cavities in selachians and in reptiles.
Their relation to the somites is undetermined. In man very
transitory structures of this nature have been reported (Zimmer-
mann, Ueber Kopfhohlenrudimente beim Menschen, Arch. f. mikr.
Anat., 1898, vol. liii), but they are rare and play no essential part
in development.

The dorsal portion of the lateral mesoderm plate of the trunk
is continued anteriorly into the branchial region, where it gives
rise to the mesenchjTne of the branchial arches and partly also
to that of the head. Ventral to the branchial arches the lateral
mesoderm of the trunk is continued into the pericardial mesoderm.
The coelom does not extend into the branchial region of the lateral
mesoderm of the head.

(f) Origin of the Connective Tissues.

From the mesenchyme, derived in part directly from the
primitive embryonic mesodermic tissue, in part from somites
differentiated from this primitive tissue, and in part from the
primitve streak, there arses a syncytial tissue which in turn gives
origin to the various connective tissues and skeletal structures of
the body as well as to some other structures, for instance, muscles
and blood-vessels.

In the adult connective tissues the bulk of the tissue substance
is usually described as extracellular.^ The chief problem for those
who have studied the histogenesis of the connective tissues has
been to determine whether the substances which are intercellular
in the differentiated tissues have an intracellular or an inter-
cellular origin. The weight of evidence seems at present to be
decidedly in favor of the intracellular origin (Fleming, 1891, 1897,
1902, Retterer, 1892-1906, Spuler, 1897, Mall, 1902, and Spalteholz,
1906). Among recent investigators who believe that the connective-
tissue fibres have an intercellular origin may be mentioned E.
Laguesse (1903) and Fr. Merkel (1895, 1909).^ Golowinski, while
contending that the fibres appear between the cells, admits that
they rise close to the cell body. According to him, most investiga-
tors have described essentially the same phenomena, but some con-
sider the mother substance in which the fibres arise as ectoplasm,
while others consider it an intercellular substance. The majority
of those who adopt the view that the ** intercellular" portions of
the adult connective tissues are intracellular in origin describe
the primitive mesenchymal cells as becoming differentiated into
endoplasmic and ectoplasmic portions. In the ectoplasm the

* Spalteholz (Anat. Anz., 1906) has, however, shown tliat even in the adult
many, if not all, of the fibrils have an intracellular position.

HISTOGENESIS OF THE CONNECTIVE TISSUES. 299

intercellular elements characteristic of each of the various kinds
of connective tissue are differentiated while the endoplasm becomes
<5onverted into the cells of the adult tissue. Retterer (1892-1906)
gives a different description of the process. According to him
the primitive tissue from which the various kinds of connective
tissue are differentiated consists of a homogeneous syncytium
in which nuclei are scattered about. This homogeneous syncytium
becomes differentiated into two parts, a hyaloplasm and a granular
chromophilic portion. The granular chromophilic portion sur-
rounds the nuclei and gives rise to branching processes which
anastomose so as ultimately to form an extensive network. The
hyaloplasm lies in the meshes of this network. The fibres of
recticulum, elastic fibres, and the branched anastomosing processes
which fill the canaliculi of bone arise from the chromophilic net-
work, while white fibrous tissue and the chief part of the ground
substance of cartilage and of bone are differentiated from the
hyaloplasm.

Recently still another view of the origin of the fibrils of the
c'onnective tissues has been advanced. It has been known for some
time that in the vitreous humor before the entrance of blood-vessels
and mesenchyme cells there exists a fibrillar structure the compo-
nents of which may be looked upon as branched anastomosing
processes of cells of the retina and lens. From this fibrillar net-
work the fibrils of the adult vitreous humor are probably derived.
Aurel V. Szily (1908) has described a fibrous network filling in
spaces throughout the embryonic body before the origin of the
mesenchyme. The fibrils of the network are branched anasto-
mosing processes of the epithelial layers bounding the various
cavities. Szily thinks that when the mesenchjTne cells arise they
wander into meshes of this fibrillar network and enter into intimate
relations with the component fibrils. The fibrils subsequently lose
connections with the epithelial cells from which they arise.
According to Szily the fibrils of the early embryonic syncytium are
thus of epithelial origin, while the cell protoplasm is of the mesen-
chymal origin. Although the early connective-tissue fibrils are
thus according to this view of epithelial origin, at a later stage
connective-tissue fibrils are also differentiated in the ectoplasm
of cells derived from the mesenchyme. According to Retterer
(1904 and 1906) the syncytium of the cutis arises partly from the
epidermis.

The following account of the origin of the connective tissues
is based chiefly on the paper of Mall, who has taken up the problem
in connection with the pig and man.

At an early stage there appear to be many individual cells
in the mesenchyme which multiply rapidly, so that in certain
regions the nuclei are closely packed together. Then the cells

300 HUMAN EMBRYOLOGY.

unite to form a syncytium and the protoplasm of the syncytium
increases more rapidly in amount than the nuclei, so that the latter
appear more widely separated from one another than at first. The
nuclei at an early stage lie within the protoplasm of the syn-
cytium, but gradually diflferentiation takes place. Immediately
about the nuclei the protoplasm becomes granular and forms an
endoplasm which is distinct from the rest of the syncytium or
ectoplasm. From the granular endoplasm about the nuclei
processes may extend into the surrounding ectoplasm. In the
ectoplasm fibrillation becomes more and more distinct. The nuclei
surrounded by the endoplasm come to lie in certain of the meshes
of the network formed by the ectoplasm. In other of the meshes
merely a fluid substance is seen. From this embryonic syncytium
the various types of connective tissue are differentiated.

Reticulum. — Reticulum seems to be the least highly differ-
entiated form of tissue which arises from the embryonic connec-
tive-tissue syncytium. The reticulum develops directly in the
syncytial ectoplasm, while the nuclei and endoplasm are converted
into cells which lie upon the reticulum fibres. In the liver the
origin of the reticulum differs from that in other parts of the
body in that it arises from Kupffer's endothelial cells instead of
from mesenchyme. The endothelial cells form a syncytium in
which the reticulum fibres are differentiated. According to Ret-
terer the reticulum fibres arise from chromophilic processes of
the perinuclear protoplasm.

White Fibrous Tissue. — ^In the development of white fibrous
tissue from the embryonic syncytium Mall distinguishes two
stages. In the first or prefibrous stage a tissue much resembling
reticulum is differentiated, in the second or fibrous stage true
white fibrous tissue appears. (Fig. 222, A and B.) In the first
stage the syncytium grows very rapidly. The ectoplasm increases
in amount much more rapidly than the endoplasm. The nuclei,
however, multiply, and the endoplasm about each nucleus becomes
drawn out spindle-like, giving rise to the well-known embryonic
bipolar cells. The tips of these cells are extended into the ecto-
plasm, and here the endoplasm appears constantly to contribute
to the ectoplasm. The ectoplasm becomes steadily more fibrillated.
The strands of ectoplasm become more and more drawn out, in
tendons and fascia? into parallel, in areolar tissue into interweaving
bundles of fibres. In the fibrous stage the embryonic fibres are
converted into true white fibrous tissue, their chemical nature
meanwhile changing. The fibres at first occasionally anastomose,
but during further development the anastomosing bridges begin
to break down. According to Mall the larger fibres become split
into the individual fibrils of white fibrous tissue. The embryonic
spindle-shaped cells become converted into the adult connective-

HISTOGENESIS OF THE CONNECTIVE TISSUES. 301

tissue corpuscles. According to Retterer the fibres in the pre-
fibrous stage belong to the chroraophilic processes of the peri-
nuclear protoplasm. On the other hand, the collagenous fibres
arise from the hyaloplasm {ectoplasm).

The body of tlie cornea is composed of a tissue the origin of
which is similar to that of white fibrous tissue. It retains more
features characteristic of the embryonic connective tissue than
does the ordinary white fibrous tissue. It contains no elastic fibres.

Pl

illuBtrato the devdopment of

Ihtconi

nective Ii»u». A. (Fig. 12. Mail.) Section thraugh the skin of (

k plK 5 cm. long. White Gbrag

ling; in the wtaplum. Magn. 250 : 1. B. (Fig. 13, Mall.) Sectjt

in through tJie skin of a pig 16

cm.bDi

1 root of a h»ir, M»gn. 2fi0 : 1.

C. (Fig.

. U, Mall.) Elaelic lijwue just beginning to appMT \a the ayncyliui

HoftheumbiliiaJveinofapig

jng. Mngn. 260 : 1. I). (Fig. 10, Mall.) Section through tlie ot

.he syneytium. Hagn, 250 : 1.

E. {Fig

. 11, Man.) Section thixiugh the frontal bone of a pig 20 mm. long

. Miign. 250 : 1.

Elastic Tissue. — With the exception of the tissue of the
cornea probably all white fibrous tissue contains a greater or less
number of elastic fibres intermingled with the bundles of white
fibrils. The elastic-tissue fibres apparently are differentiated .
directly in the same syncytial ectoplasm in which the bundles of
white fibrils develop (Fig. 222, C). The youngest pigs in which
Mall found elastic fibres were four centimetres long. Tliese fibres
were found in the aorta and neighboring arteries. Fenestrated
membranes are formed by the coalescence of neighboring fibres.
Spalteholz (1906) has found elastic fibres in the truncus arteriosus
of pig embryos 9.2 mm. long. Ranvier held that elastic fibres
arise from the fusion of rows of elastic granules. According to
Mall, elastic fibres are never formed by the fusion of rows of
such granules. Spalteholz has likewise found that the elastic

302 HUMAN EMBRYOLOGY.

fibres are directly diflferentiated. According to Eetterer, the
elastic fibres arise in the perinuclear chroraophilic protoplasm
and from the chromophilic processes which spring from it.

Adipose Tissue. — Adipose tissue appears in the fourth month
in the human embrj^o. In the regions where the adipose tissue is
formed the embryonic mesenchymal tissue becomes differentiated
on the one hand into blood-vessels and a supporting fibrous-tissue
framework, on the other into cells in the protoplasm of which
granules of fat appear. The granules of fat in each cell gradually
become consolidated, so that finally there arises a single large
globule of fat which greatly distends the cell. The protoplasm of
the cell now forms a thin covering for the globule of fat. The
nucleus surrounded by a small amount of granular protoplasm lies
at one side. The fat cells are arranged more or less definitely
with relation to the blood-vessels and frequently form well-marked
clusters. (See Bell, 1909.)

Cartilage. — In the formation of cartilage the ectoplasm of
the syncytium becomes more and more dense. The nuclei sur-
rounded by endoplasm come to lie in spaces in the ectoplasm, thus
forming precartilage cells which in turn become converted into
cartilage cells (Fig. 222, D). The syncytial ectoplasm undergoes
chemical changes which make it exhibit the reactions characteristic
of hyaline ground substance. Not infrequently the ectoplasm
before becoming converted into hyaline ground substance becomes
marked out into cell territories by the appearance of membranes
between the cell units. These membranes appear as fine lines in
cross section and have staining reactions similar to hyaline car-
tilage. When this condition is found, the cartilage has an epithe-
lioid appearance (cellular cartilage).

The endoplasmic units or cartilage cells exhibit a differentia-
tion into perinuclear and peripheral portions. From the peri-
pheral portion hyaline substance is differentiated so as to form
a capsule (Max Schultze). The capsule appears lighter than the
surrounding tissue and has slightly different staining reactions.
Meanwhile the endoplasm increases in amount, the nuclei multiply,
and from time to time cell division takes place in the endoplasmic
units, but this division does not extend into the surrounding ecto-
plasm. When cell division takes place, the line of separation
between the two daughter cells usually becomes marked by a fine
septal membrane composed of a substance that has some of the
staining qualities of the cell capsules. This septum then becomes
divided into two lamellae, each of which together with half of the
old capsule surrounds a daughter cell. Sometimes the capsules of
several successive generations of cells remain distinct for a con-
siderable period, so that a capsule which first surrounded a single
cell comes to surround several groups of daughter cells, each group

HISTOGENESIS OP THE CONNECTIVE TISSUES. 303

and each daughter cell having in turn a capsule of its own.
Usually, however, the primitive capsules become indistinguishably
fused with the surrounding matrix, so that capsules about single
cells or pairs of cells alone remain distinct.

Growth of cartilage is in part interstitial, in part perichondral.
The interstitial growth is due (1) to the direct increase in amount
of the ectoplasm or ground substance, (2) to the formation of
cell capsules at the periphery of the cells and the fusion of these
capsules with the matrix, and (3) to cell multiplication. Peri-
chondral chondrification is due to the formation of new cartilage
beneath the perichondrium. The ground substance increases in
amount faster than the cells multiply.^

In white-fibrous cartilage bundles of fibrils develop in the
syncytium while the hyaline substance is being deposited. In
elastic cartilage, according to Mall, elastic fibres are formed after
the hyaline substance has been differentiated. According to
Spalteholz (1906), however, elastic fibres appear before the hyaline
ground substance in the ear cartilage of the pig. In the arytenoid
cartilage clumps of elastic granules are deposited. While Eanvier
held that elastic fibres arise from the fusion of rows of these
granules. Mall, as mentioned above, believes that neither here nor
elsewhere are the elastic granules fused to form elastic fibres.

Bone. — The histological structure of bone is still a matter of
dispute. Most investigators seem to consider the ground sub-
stance to be composed of bundles of fibrils resembling those of
white fibrous connective tissue embedded in a homogeneous
** cement" substance. V. KoUiker, who considered the cement sub-
stance to be slight in amount, believed the calcium salts to be
embedded both in this and in the fibrils. V. Ebner, 1875, believed
the calcium salts to be embedded chiefly in the cement substance.
Eetterer, 1905 and 1906, believes the ground substance of bone to
be composed of a chromophilic reticulum embedded in a hyalo-
plasm impregnated with calcium salts. It is well known that
the ground substance of bone contains a collagenous substance
similar to that of white fibrous tissue.

Bone, like other connective tissues, is formed from a blastemal
syncytium. Ectoplasm becomes distinct from nucleated endo-
plasmic cell units. In the ectoplasm calcium salts are deposited.
Two stages may thus be distinguished, — a pre-osseous, previous
to the deposition of calcium salts, and an osseous, after these salts
have been deposited. During ossification about two parts of inor-
ganic salts combine with one part of organic matter.

The cells which give rise to bone may appear similar to
ordinary immature connective tissue cells or they may pass

*For details concerning the development of cartilage see Retterer (1900).

304 HUMAN EMBRYOLOGY.

through a stage in which they appear epithelioid in character.
Cells of the latter type are frequently found in regions where
layers of bone are being applied to pre-existing bone or to calcified
cartilage. The epithelioid cells, which Gegenbaur called osteo-
blasts, form a layer from the deep surface of which certain cells
branch, anastomose, and give rise to an osteogenetic syncytium
which becomes converted into bone (Fig. 223, A).

According to v. Kolliker (Gewebelehre) and to many other
investigators, the osteoblasts secrete the ground substance, which,
therefore, is to be looked upon rather as intercellular than as
intracellular. To Waldeyer (1865) we are indebted for the first
clear description of the differentiation of the ground substance of
bone in the peripheral protoplasm of the osteoblasts.

The endoplasmic units, or bone corpuscles, have branched
processes which anastomose freely through the canaliculi with
those of neighboring cells. Before birth (Neumann) the periphery
of the bone corpuscles becomes differentiated into a resistant
cuticle which has staining reactions similar to elastic tissue (Ret-
terer) and which is resistant to strong acids and alkalies. Brosike
(1885) considered this cuticle (bone-cell capsule) to be composed
of keratin, but Kolliker has shown it to be soluble in boiling water.
According to Eetterer the protoplasm of the branching processes
which lie in the canaliculi is converted into a similar substance.

In the human embryo bone arises chiefly in connection with a
transitory cartilaginous skeleton which it gradually in large part
replaces. Thus the vertebrae, ribs, sternum, the skeleton of the
extremities, and most of the base of the skull are first formed of
cartilage, and the cartilage is later replaced by bone (substitution
bone). Centres of ossification may appear within the cartilage
(endochondral ossification) or beneath the perichondrium (sub-
periosteal ossification). On the other hand, most of the bones of
the face and the flat bones of the skull are formed directly in
membranous tissue (intramembranous bone).

When bone is first formed in the embryo, it consists of a
eoarse plexiform or spongy framework, in the meshes of which
lies a vascular embryonic marrow. To the walls of the spaces in
this primitive spongy bone successive layers of bone are added
by osteoblasts, so that the spaces come to have lamellated walls.
Similarly beneath the periosteum lamellae of bone are laid down,
so that the surface of the bone comes to consist of a series of suc-
cessive lamellae. The formation of definite lamellae of compact
bone is not, however, well marked until after birth. Previous to
this period the vascular spaces in the bone are relatively large,
so that the coarse spongy structure mentioned above is long
retained. In long bones Schwalbe found compact lamellar bone
formed about the marrow cavity and in the Haversian canals in

HISTOGENESIS OF THE CONNECTIVE TISSUES.

laeath th

E pfrio»leumi 2, osteoblast!! with reticular

mm

iBctive tissue (01 in a ^edullc

jone; 3,1

layer of preovieoue tiuiue; 4, DUcltwled. gran

iBiaina; v. blood-vessel. B. (After Siymo

Of the femur c

A a rabbi

Vol.

I.— 20

306 HUMAN EMBRYOLOGY.

the sixth month after birth, but beneath the periosteum not until
the fourth year. Kolliker (Gewebelehre) found lamellar subperi-
osteal bone as early as in the first year after birth.

During the period of the growth of bone new bony tissue is
being constantly added in some regions, while in other regions
the bone already formed is absorbed to make way for new vascular
marrow cavities. In this process of bone absorption large cells,
osteoclasts, containing, according to v. Kolliker who first described
them, from one to sixty nuclei, play a chief part (Fig. 223, B).
These osteoclasts vary in size, being from 43 to 91 /* long, 30 to
40 M wide, and 16 to 17 fi thick. They apparently have the power
of dissolving bone or calcified cartilage. The depressions which
they cause in bone are called Howship's lacunae. According to
Kolliker, they arise from osteoblasts, and may again divide up
into osteoblasts or after remaining for a greater or less length of
time in the bone marrow they may disappear. The nuclei within
the cell multiply by direct division. The changes of form which
bones undergo through the process of growth by apposition of
new layers of bone to pre-existing layers and the absorption of
bone previously laid down are well illustrated by comparing the
jaw of the infant with that of the adult (Fig. 224, C).

Under the term Sharpey's fibres, according to Eetterer (1906),
several distinct structures have been described: (a) prolonga-
tion of the periosteum into the bone; (b) granular elastic proto-
plasmic processes of the lamellar system; (c) portions of the bone
in which calcium salts have disappeared from the hyaloplasm and
fibrous tissue has been differentiated. The true Sharpey's fibres
are probably prolongations of the periosteum left behind as suc-
cessive layers of bone are differentiated beneath the periosteum.

To this brief description of the general nature of the process
of ossification we may add a short account of the special features
which characterize intramembranous, subperiosteal, and endo-
chondral types of ossification.

Intramembranous Ossification (Fig. 222, E, Fig. 224). — ^In
this type of ossification bone first appears in the form of a network
of spicules interwoven with a network of blood-vessels. Ossifica-
tion begins at a centre from which it radiates peripherally. As
one passes from the centre towards the periphery in the early
period of ossification, one finds all stages from fully formed bone
to an undifferentiated embryonic connective- tissue syncytium. In
ossification in very young embryos the connective- tissue syncytium
appears to be directly transformed into bone. The transforma-
tion is marked first by the fibrils of the ectoplasm becoming more
clearly marked, and then by the appearance of a basophilic sub-
stance in the ectoplasm. In older embryos the ectoplasm is, accord-
ing to Mall (1906), transformed into prefibrous tissue and the

HISTOGENESIS OP THE CONiNECTIVE TISSUES.

Bone corpuKclca Oit«ob1»-''ts

It)

Fia. 224.— A. (Aft« Stj-monowi

with IhaCofsnulull

ok of HiBloloe)-, tran,'. hv MarCalluni. Fin. I
an fetus. B. (Quaiii, afler Sharpey. Quain'
K fFlal shwp. Siteolfetii!-2i in. Masn. a
iker. Gewebelehre. Fig. a"!.)

308 HUMAN EMBRYOLOGY.

latter is transformed into bone. The diameter of the embryonic
bone corpuscles, according to v. Kolliker, varies from 13 to 22 f^.

The primitive plexiform bone is thickened by deposit of
osseous substance beneath tlie periosteum. The latter appears
soon after bone-formation has commenced. The spaces in the
plexiform network of bone at an early stage become converted into
canals containing blood-vessels and primitive marrow.

In bone of membranous origin cartilage may subsequently be
developed beneath the periosteum. Examples of this are to be
found in the temporomandibular joint.

HyfJine ortilice

Pia. 225. A.— (After Siymonowici, Text-book ol Histology, tmnslated by MiwCi>Uum, Fig. 103.)
From B longitudinal neclion of * faigrr of & tlirBe-and-«-halt-montlia human fetus. Two-thirds oJ the
second phftlbox are repreeeuted. At X a periosteal bud is to be seen. Magn. about 85 : I-

Subperiosteal Ossification (Fig. 225, A and B). — Bone is
formed in the deep layer of the periosteum (perichondrium) essen-
tially as bone is formed in membrane which is not closely applied
to cartilage. The bone formed beneath the periosteum has at first
a coarse plexiform structure. The meshes of the osseous frame-
work enclose vascular embryonic marrow. As mentioned above,
dense subperiosteal lamellst are formed in human long bones in
the first year after birth, according to Kolliker (Gewebelehre),
while according to Schwalbe they are not formed until the fourth

HISTOGENESIS OF THE CONNECTIVE TISSUES. 309

year. Subperiosteal ossification is the sole method of substitutioa
of osseous for cartilaginous tissue in some of the bones (in the
ribs, for example), while in others it is closely associated with
endochondral ossification (diaphyses of the long bones). When it
is the sole method of ossification, the underlying cartilage fre-
quently undergoes changes similar to those preceding endochon-
dral ossification (see below).

Fio. 22fi, B. — (Afor Siymonowic., Teit-book of HinWlogy, tmoJiliWd by MMC»llum. Fig. 196.)
From » lonsitiidiaal nection of a tinger of a four-moDths huioBD fitiu. Only tbfl diaphysis of the sacond
phalanx is rtpreMnt«d. Mien, about 86 : 1.

Endochondral Ossification. — In endochondral ossification
processes from the osteogenic layer of the perichondrium, or
periosteum, extend into the substance of tlie cartilage, and these
give rise on the one hand to destructive activities which break
down the cartilage and on the other to constructive activities which
result in the formation of bone. Endochondral ossification is pre-
ceded by well-marked changes in the cartilage (Fig. 225). The
cartilage cells first multiply rapidly in number and then enlarge
so that the matrix becomes relatively reduced in amount. Neigh-

310 HUMAN EMBRYOLOGY.

boring cartilage cells may so expand that the matrix between them
disappears. Meanwhile calcium salts are deposited in the matrix
in the form of granules which may become confluent. The proc-
esses from the periosteum break into the cavities occupied by the
cartilage cells, enlarge them, and thus give rise to primary marrow
cavities. In the phalanges and other long bones of limited size,
the cartilage at the centre of the shaft may be completely absorbed
before the endochondral ossification begins. The primitive
marrow is vascular and contains an embryonic syncytium not
highly differentiated. Osteoblasts and osteoclasts and embryonic
connective tissue, however, appear in it at an early stage, fat and
marrow cells at a later period. About the primitive marrow cavi-
ties bone is quickly laid down and there thus arises spongy endo-
chondral bone. The bone first laid down is later again absorbed
during development of the larger central marrow cavities. From
the cavities into which the marrow first penetrates it gradually
extends into neighboring cartilage-cell spaces. As the osteogenic
tissue spreads, the surrounding cartilage undergoes changes simi-
lar to those which took place at the primary centre of ossification.
Thus, so long as the process of ossification continues, the cartilage
farthest removed from the centre of ossification shows the least
modification from the type of primitive hyaline cartilage, while as
one passes toward the centre of ossification one finds the successive
changes of cell multiplication, cell expansion, and calcification of
the matrix. In long bones these successive stages are especially
well marked. The multiplication of cartilage cells gives rise to
groups which become arranged in long columns which are parallel
to the long axis of the bone. The boundary between the zone of
ossification and that of the highly modified cartilage is usually
fairly sharp (Fig. 225, B). Capillary loops extend close to the
limit of the advancing ossification. The extremities of these
loops are often dilated.

The fate of the cartilage cells in the calcified matrix is still
in dispute. Most modem investigators, including Kolliker
( Gewebelehre, 1889), seem to follow Sharpey and Loven in con-
<;luding that the cartilage cells are destroyed as osteogenic tissue
derived indirectly from the periosteum enters the cell spaces.
Numerous accurate observers, however, among who may be men-
tioned H. Muller (1859), Ranvier (1865), and Retterer (1900),
T)elieve that the cartilage cells become converted into osteogenic
tissue, each cartilage cell giving rise to several smaller cells and
to reticular tissue. The old view, that cartilage may become
directly converted into bone, seems to have few modern adherents.*

* According to Strelzoff (1873), this metaplasia is constant in some regions,
for example, in the lower jaw of human embryos.

HISTOGENESIS OF THE CONNECTIVE TISSUES. 311

In epiphyses centres of ossification arise at a comparatively
late period. Blood-vessels, which spring from the periosteum and
from the bone marrow, penetrate into the epiphyseal cartilage
long before ossification begins. Friedlander (1904) gives good
pictures of the blood-vessels in the epiphyseal cartilages of the
long bones. In some cartilages the blood-vessels appear in the
third fetal month. In the seventh all the larger cartilaginous areas
show rich vascular plexuses.

Growth of Bone. — The question as to whether or not there is
an interstitial growth of bone has given rise to extensive investiga-
tions. The evidence is fairly conclusive that there is no well-
marked interstitial growth in bone. Hales, Duhamel, John Hunter,
and others showed, during the eighteenth century, that two pegs
driven into a bone do not move apart during development unless
there is a non-ossified region between the two pegs. Z. G. StrelzoflF
(1873), however, brought forward a certain amount of evidence
to show that under some circumstances there may be a slight inter-
stitial growth of bone.^ Experiments made with madder go to
show that growth of bone takes place entirely by apposition.
Madder stains newly forming bone, and by feeding it to young
animals the successive applications of layers of bone may be
followed. Experiments along this line were first performed by
Duhamel and J. Hunter. Duhamel also showed that a ring placed
on the outside of a long bone of a young animal may eventually
be found in the marrow cavity.

Regeneration. — In case of fractures union is effected by osteo-
blasts which give rise to new bone which unites the broken
ends. These osteoblasts in young animals may apparently
be derived either from the marrow or from the periosteum, but
in the adult chiefly, if not wholly, from the periosteum. Bonome
(1885) has, however, brought forward evidence to show that the
bone corpuscles in certain conditions where they are supplied with
abundant nutrient blood may give rise to osteoblasts. Not infre-
quently temporary cartilage is produced in places at the site of
the fracture. In man fibrous tissue is often produced if the broken
ends of the fractured bone are not closely approximated. The
experiments of Oilier and others have shown that the bone-forming
power of the periosteum may be exercised even when this is trans-
planted into the tissues at some distance removed from any bone.
If the periosteum is preserved it has the power of restoring in
nearly normal form large parts of bone.

See also Egger (1885) and J. Wolff (1885).

312 HUMAN EMBRYOLOGY.

ADDENDUM.

Since the preceding section on the development of the connective tissues
was written, there have appeared several important articles on the development
of the connective tissues in mammals. Fr, Merkel (1909) brings forth new
evidence in favor of the intercellular origin of the connective-tissue fibrils. He
pays particular attention to the development of limiting membranes which in places
sharply mark off epithelium from the underlying connective tissue. These mem-
branes, according to Merkel, arise from the connective-tissue matrix independently
of the connective-tissue cells. They may become fibrillated. Similar non-cellular
connective-tissue substances are formed at an early stage in the septa between
myotomes, and later between muscle cells of various types and in lamellated
connective tissues. The sarcolemma of striated muscle cells has a similar origin,
according to Merkel. Disse (1909), on the other hand, describes the osteogenetic
tissue as arising from the cell protoplasm. Each osteoblast becomes divided into
two parts, a perinuclear granular portion and a peripheral, usually basilar, hyaline
portion. The hyaline substance derived from osteoblasts fuses to form a mass in
which fibrils differentiate after the hyaline substance is separated from the peri-
nuclear protoplasm. Bell (1909) gives a clear description of the development of
adipose tissue. He supports the view of the histogenesis of the connective tissues
adopted by Mall.

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316 HUMAN EMBRYOLOGY.

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302 bis 324. 189L

PART II.
Morphogenesis of the Skeletal System.

A. GENERAL FEATURES.

The definitive skeletal system is composed of bones and car-
tilages united to one another at joints by means of ligaments. In
the lowest vertebrates a cellular rod, the chorda dorsalis or noto-
chord, situated in the mid-axial line ventral to the central nervous
system, constitutes the chief part of the axial skeleton. In the
higher vertebrates a chorda dorsalis is also formed during early
embryonic development, though in mammals and man it lends
little or no skeletal support to the embryo and mere derivatives of
it are to be found in the adult. The definitive skeleton of the

MORPHOGENESIS OF THE SKELETAL SYSTEM. 317

higher vertebrates, including man, is differentiated from the
mesenchyme of the head, trunk, and limbs. The process of differ-
entiation is somewhat complex. As a rule, the first visible step in
the process is marked by condensation in the sclerogenous mesen-
chyme or scleroblastema. Thus, in the development of the skele-
ton of the inferior extremity, condensation begins in the vicinity of
the future hip-joint and from here extends distally and proximally,
so that there is produced a continuous mass of condensed tissue in
which pelvic, femoral, tibio-fibular, and tarsal regions and five
metatarso-phalangeal rays may be distinguished. The hard parts
of the skeleton are developed from centres which appear in the
scleroblastema. The joints are developed in the scleroblastema
which intervenes between the hard parts.

THE BONES.

It has been mentioned in the section on histogenesis that most
of the bones of the body are first formed of cartilage and then,
during subsequent development, bone is gi*adually substituted
for cartilage, substitution or cartilaginous bones (Figs. 277 and
278). Other bones are formed directly in the membranous sclero-
blastema, membrane or investment bones. The bones of the
extremities, with the partial exception of the clavicle, the bones
of the spinal column and thorax, and the greater part of those
of the base of the cranium, have a chondrogenous origin. The
greater part of the bones of the cranial vault and of the face
arise directly in the scleroblastema.

It is to be noted, however, that during the formation of many
of the typical substitution bones ossification may extend into
membranes attached to the cartilage, so that certain processes on
these bones are membranous in origin, and that, on the other
hand, certain parts of bones of membranous origin may second-
arily give rise to cartilage (temporomandibular joint). Several of
the definitive bones of the skull have an origin partly cartilaginous,
partly membranous.

SUBSTITUTION BONES.

As a rule, a centre of chondrification appears in the midst of
condensed scleroblastema. (See femur, tibia, and fibula, Fig. 275.)
It may, however, appear in tissue but slightly condensed, as in
case of the vertebral bodies. Fig. 273.

The cartilaginous centres expand rapidly, both by apposition
from the surrounding blastema and by interstitial growth. Neigh-
boring centres are thus soon brought into close approximation.
Some of the centres fuse with one another in the region of approxi-
mation. Between other centres joints are developed. The fate

318 HUMAN EMBRYOLOGY.

of the cartilaginous centres, therefore, differs considerably in
different regions.

The conditions in the skeleton of the limbs are the simplest.
Here for each of the bones, including the pubis, ischium, and ilium,
there is a single centre of chondrification (see Fig. 226 and Figs.
275 and 276). The clavicle forms an exception to the other bones
in that the tissue at the centre of chondrification is not converted
into typical embryonic hyaline cartilage (see pp. 380 and 388).
The centres of chondrification for the pubis, ischium, and ilium
soon fuse with one another so as to produce a continuous carti-
laginous hip-bone, which gradually assumes definitive form (Figs.
276, 277, and 278). With the exception of a few cartilages in
the wrist, the fate of which is treated elsewhere (p. 383), each of the
other embryonic limb cartilages undergoes an independent develop-
ment. In the region of the knee-joint, however, and possibly in
some other articular regions of the limbs, independent skeletal
elements become at an early period temporarily fused together
by a kind of precartilage (Fig. 283). Temporary joints of this
kind resemble the permanent joints of the shark's fin.

A centre of ossification appears ia the main body of each of
the cartilages of the skeleton of the limbs; in most of them early
in fetal development, but not until after birth in those of the ankle
and wrist, with the exception of the calcaneus, talus and cuboid
and in the patella and other sessamoid bones. These chief centres
of ossification establish bone in place of cartilage as growth pro-
ceeds. In case of all the limb bones except those of the ankle and
wrist secondary epiphyseal centres of ossification appear early in
childhood in those portions of the bone still cartilaginous, and as
maturity is approached become fused with the main part of the
bone. Growth in length of bone, as stated in the section on his-
togenesis (p. 311), is dependent upon the growth of the cartila-
ginous matrix and ceases when the epiphyses become fused with
the main body of the bone. In the adult limb skeleton the only
cartilage remaining is that upon the joint surfaces of the bones.

In the vertebral columyi there are two bilaterally placed
centres of chondrification for the body of each vertebra and one
for each half arch (Figs. 239 and 249). The arch cartilages join
the body considerably before they unite dorsally so as to complete
the arch about the spinal cord. The ribs develop from separate
centres of chondrification and do not fuse with the bodies. In the
cervical, lumbar, and sacral regions there are more or less distinct
centres of chondrification of costal elements which quickly fuse
with the cartilage of the body. In the sacral region the various
cartilages fuse to form a cartilaginous sacrum. The cartilaginous
vertebral bodies are at first separated by thick blastemal discs,
but as development proceeds the discs near the centre become thin

MORPHOGENESIS OF THE SKELETAL SYSTEM. 319

and partially converted into a precartilaginous tissue, so that for
a brief period there is a continuous vertebral axis composed of
tissue of a cartilaginous nature but in which segmentation is
clearly marked.

The cartilage of the sternum arises mainly from the cartilage
of the ribs, from which it is secondarily separated by the formation
of costosternal joints.

There are primary centres of ossification for the bodies of the
vertebrae, each half arch, the ribs, and some of the costal elements
of the sacrum. In addition, there are many epiphyseal centres.

In the cranial blastema numerous centres of chondrification
appear (Figs. 310 and 311). These, however, fuse to form a con-
tinuous chondrocranium, in which no blastemal sutures remain to
separate one cartilaginous element from another (Figs. 312 and
313). The incus and stapes remain distinct cartilages. The
malleus is long continuous with Meckel's cartilage, the cartila-
ginous skeleton of the mandibular arch. The cartilage of the
hyoid arch becomes attached to the chondrocranium.

While the chondrocranium is being formed, centres of ossifi-
cation begin to appear in various parts of the cranial scleroblas-
tema. From these centres of ossification, partly by expansion and
partly by fusion of neighboring centres, there are produced the
membranous bones of the skull (Fig. 321). Meanwhile, centres
of ossification appear in the chondrocranium and by expansion and
fusion give rise to the substitution bones of the skull. In the
definitive skull some bones, like the parietal, frontal, and maxil-
lary, are purely membranous in origin. Some, like the ethmoid,
hyoid, incus, and stapes, are fairly typical substitution bones,
while many of the bones, like the occipital, sphenoid, and temporal
bones, arise partly from centres which appear in membranous
tissue, partly from centres which appear in the chondrocranium.
In the membranous tissue in which the centres for the investment
bones appear the definitive form of the skeletal part is much less
clearly marked than in the chondrocranium (compare Figs. 310,
311, 312, 313, 321).

CARTILAGES.

Not all the cartilage of the embryonic skeleton becomes re-
placed by bones. Some of the embryonic cartilages become reduced
to fibrous tissue, as in the case of the stylohyoid ligament; some
give origin to the cartilages of the definitive skeleton, such as the
costal cartilages and parts of the nasal capsule; some merely
disappear.

320 HUMAN EMBRYOLOGY.

JOINTS.

When first diiferentiated the fixed parts of the skeleton are
united to one another by dense blastemal tissue in which little
definite form is to be observed. In ease of synarthroses this inter-
vening blastemal tissue becomes directly or indirectly transformed
into fibrous tissue (syndesmosis), into cartilage (synchondrosis),
or into bone (sjTiostosis). While, as a rule, the fibrous tissue of a
syndesmosis comes fairly directly from the primitive blastema
of the embryonic joint, it may arise as the result of retrograde
metamorphosis of cartilage (lig. stylohyoideum). A synchon-
drosis is usually preceded by an embryonic blastemal syndesmosis.
A synostosis is usually preceded by a sjnidesmosis or a synchon-
drosis.®

In a diarthrosis the joint cavity, synovial membrane, and the
various ligaments characteristic of the joint are diiferentiated
from the dense blastemal tissue which unites at first the two
embryonic cartilages entering into the joint. Disci articulares and
menisci articulares are also diiferentiated from this blastema.

In case of the few diarthroses formed between membrane
bones, as for instance between the mandible and the temporal bone,
the blastemal tissue has the power of giving rise to cartilage which
covers the joint surfaces of the bones.

The various steps in the diiferentiation of a simple diarthrosis
are well illustrated in the digital articulations (Figs. 226-228).
In Fig. 226 are shown the cartilaginous anlages (a) of the three
phalanges and the distal part of the metacarpal of a finger of an
embryo 2.7 cm. long. These cartilaginous anlages are embedded in
a dense blastema which shows lighter areas in the vicinity of the
future joints (c). The term intermediate zone has been applied
to the dense tissue lying between the two cartilages entering into a
joint (6). As the cartilages expand they come into close approx-
imation, as shown in the finger of a fetus 7 cm. long (Fig. 227).
At this stage the cartilage is undergoing changes preliminary to
ossification. The perichondrium about the joint surfaces of the
cartilage entering into the joint is very dense. The joint cavity
first appears at the periphery of the joint (Fig. 227). Gradually
it extends in between the two cartilages entering into the joint
and a variable distance over the head toward the shaft (Fig. 228,
A, B, C). The form of the joint surfaces of the bones entering
into the joint is highly diiferentiated before the joint cavity
appears (Fig. 227).

In the more complex joints in which menisci or intra-articular
ligaments are diiferentiated, as in the knee-joint and hip- joint

"The nucleus pulposus of the interv^ertebral fibrocartilage (disc) arises from
the tissue of the chorda dorsalis (see p. 341).

MORPHOGENESIS OF THE SKELETAL SYSTEM.

c.

FioB. 826-228.-

: of tbe middle finger r

322 HUMAN EMBRYOLOGY.

(Figs. 281, 282, 285), the cartilages of the bones entering into the
joint are less closely approximated at the time of the formation of
the joint cavity than in simple joints, like those of the fingers.
The external ligaments and the various intra-articular structures
are differentiated directly from the intermediate zone of blastema,
while the blastemal tissue next the joint surfaces of the cartilages
entering into the joint becomes condensed into a dense perichon-
drium. The rest of the tissue becomes less dense in character and
is converted into mucoid tissue with a few cells scattered through
the matrix (Fig. 282). As in all diarthroses the formation of
the joint cavity begins at the side and extends toward the centre
of the joint. The definitive cavity may be formed by the fusion of
several cavities which appear at various places in the periphery
of the joint (knee-joint, p. 372). The mucoid tissue disappears as
the joint cavity enlarges.

The capsular ligament which is formed from the periphery of
the intermediate blastemal zone is continuous on each side of the
joint at first with the perichondrium and later with the periosteum.
The synovial membrane is formed on the inner surface of the
capsular ligament. Synovial villi arise in the latter part of fetal life-

At the time of the appearance of the joint cavity the bones
entering into the joint are composed of cartilage in the region of
the articulation, although ossification may be well under way at
some distance from the articulation (Figs. 227 and 228). After
the appearance of the joint cavity the articulating parts undergo
an elaboration in form (Fig. 228), which may be quite extensive
(Figs. 286, 288). This elaboration of form is due not only to
interstitial growth of cartilage, but also to the appositional
growth of bone. As the result of the ossification, all the cartilage
near the joint becomes entirely replaced by bone except on the
joint surface, where, as a rule, a layer of hyaline cartilage remains
throughout life. The thin, dense layer of blastemal perichondrium
which for a short time covers the joint cartilage, as a rule dis-
appears early, although it may give rise to a permanent film of
tissue or the joint cartilage may become in part composed of
fibrocartilage ( sternoclavicular, temperomandibular, costoverte-
bral, sternocostal articulations).

The relative positions of the articulating bones vary greatly
in different regions at the time of the formation of the joints. The
knee- and elbow- joints, for instance, are flexed at an angle of
about 90"^ while the wrist-joint is nearly straight.

SESAMOID BONES.

Tendons are closely fused to the joint capsule in many articu-
lations of the extremities. In certain regions where this occurs
sesamoid bones are developed. The largest of the sesamoid bones.

MORPHOGENESIS OF THE SKELETAL SYSTEM. 323

is the patella. Well-marked sesamoid bones are found regularly
on the flexor side of the metacarpo- and metatarsophalangeal
joints, usually of the first and frequently of the other digits of
the hand and foot. Dorsally placed sesamoid bones have also been
seen in connection with the thumb. On the flexor surface of the
thumb a sesamoid bone is frequently found at the inter phalangeal
joint. Fibrous interphalangeal sesamoids have been found in
connection with the fingers. The sesamoid bones are better devel-
oped in some of the lower mammals than in man, and, according to
Pfitzner, are more frequent in the human embryo than in the
adult. They are developed at the periphery of the intermediate
blastemal zone. The blastema becomes condensed, and then in the
better marked sesamoid bones becomes gradually transformed into
cartilage. Ossification takes place relatively late in childhood. On
the intracapsular origin of the sesamoid bones see Bradley (1906).
In some tendons not intimately connected with a joint capsule
a sesamoid bone may be developed in a region where the tendon is
subjected to stress against a bone about which it turns. An
example is the sesamoid bone often found in the tendon of the
peroneus longus where this plays over the tuberosity of the cuboid.
According to Lunghetti (1906), the sesamoid bone in the tendon of
the M. peroneus longus develops in fibrous connective tissue, not
in cartilage. It is commonly stated that it passes through a fibro-
cartilaginous stage before becoming ossified.

VARIATION IN THE DEVELOPMENT OP THE SKELETON.

Variations in the bones of the adult human skeleton are frequent. Thus,
for instance, skeletons with only eleven or with thirteen free ribs are not uncommon.
Rosenberg, Pfitzner, Thilenius, and others would ascribe some of the variations
found in the adult skeleton to the chance persistence of transitory conditions
normally present in the embryonic or fetal skeleton and supposedly of phylogenetie
importance.

The studies of Thilenius, Bardeen, Mall, and others have shown, however^
that the skeleton of the embryo is subject to fluctuating variations like those
found in the adult. At present there are not sufficient data to determine definitely
the relative frequency of skeletal variations in the adult compared with those
in the embryo or fetus.

ABNORMALITIES IN THE DEVELOPMENT OP THE SKELETON.

The form of the skeleton as a whole and of the individual bones which
compose it depends partly upon heredity, partly upon the mechanical and chemical
influences to which it is subject during growth. The variations which are a
normal inheritance of the race, including such extreme forms as individuals with
six toes or six fingers, are to be distinguished from the abnormalities of structure
due to unfavorable environment either within or without the body. In the main
the shapes of the bones and joints are inherited, but to some slight extent both
bones and joints are moulded by the experience of the indiridual. Abnormal
stress of muscular or other origin, and abnormal lack of stress, as in cases of
muscle paralysis, both give rise to bones and joints abnormal in form.

324 HUMAN EMBRYOLOGY.

During development the skeleton is markedly influenced by internal chemical
conditions affecting the growth or general nutrition of the body. The skeleton
in some cases seems to be the part primarily affected. The skeletal lesions vary
all the way from a retardation in the time of appearance of centres of ossification
to the failure of a part of the skeleton to develop or to hyperplasia and abnormal
form-differentiation.

Agenesis, or failure of skeletal development, may be due either to primary
lack of origin of a part or to an affection which destroys the skeletal anlage
after it has begun to differentiate. It is most frequently found in the cranial
vault and in the vertebral arches, less frequently in the vertebral bodies and
the bones of the extremities. The osseous defect is usually, but not always,
associated with other marked physical deformities.

Hypoplasia, underdevelopment, of the skeleton, whether generalized or eon-
fined to a part, may be due either to prenatal or to postnatal conditions. The
failure of the bones to develop normally may be due (1) to lack of active
proliferation of cartilage (characteristic of cretins), (2) to inactivity in the
process of ossification, membranous, subperiosteal or endochondral (see Michel,
1903, Lindemann, 1903), (3) to a premature union of epiphyses with the main
part of a bone, (4) to growth of connective tissue between the growing cartilage
•of a bone and the region where ossification usually extends into the cartilage
(micromelia chondromalacia, fetal rickets), and (5) to inflammation and other
abnormal conditions affecting the growing parts of the bone.

Various congenital forms of hypoplasia are recognized, — microsomia,
micromelia, micromelia chondromalacia (fetal rickets), cretinism, etc. In most
instances while there is a general underdevelopment of the skeleton the long
bones are especially affected and appear short and relatively thick; the pelvis
and thorax are also usually abnormally smaU, and the root of the nose is broad
and not infrequently sunken in. The causative factors of these conditions are
obscure. In cretinism growth of cartilage is retarded and there is a delay in
the appearance of centres of ossification and also in the fusion of epiphyses
with the main parts of the bones (Wyss, 1900). In this disease there is good
evidence that the failure of cjevelopment of the body, including the skeleton,
is due to lack of normal secretion by the thyroid gland. It is not improbable
that the secretions of other glands of similar type may affect the development
of the skeleton. Some diseases involving both the skeleton and the hypophysis
have led to the belief that there is a relation between this gland and skeleton
development. This relation has, however, been disputed (Arnold, 1894). K.
Bach (1906) has recently discussed the apparent influence of the thjrmus on the
growth of bones.

Hyperplasia f overgrowth of the bones, is due (1) to an excessive activity of
membranous or subperiosteal ossification or (2) to a prolonged persistence of actively
growing epiphyseal cartilages, union of epiphysis with the main part of the bone
being delayed, while endochondral ossification continues beyond the usual time.

Hyperplasia may be local or general and may give rise to a well-proportioned
or to disproportionate enlargement of the skeleton. It is stated that removal
of the testicles early in infancy or congenital absence of the testicles may lead
to an excessive prolongation of the activity of the epiphyseal cartilages and
hence to gigantism (P. Launois and P. Roy, 1903, Poncet, 1903). Phosphorus
and arsenic in small doses are said to promote bone growth. Partial hyj>erplasia
is found most frequently in the skull and in the bones of the hands and feet.
An irritative stimulus, such as a blow, may excite excessive growth of bone. In
young people a small centre of inflammation (tuberculosis, osteomyelitis) in the
diaphysis may excite activity in the processes concerned in ossification and induce
abnormal growth in size of bone. If the centre of inflammation is near the epiphy-
seal cartilage, ossification is apt to be very irregular.

MORPHOGENESIS OF THE SKELETAL SYSTEM. 325

In congenital syphilis there are frequently, although not always, present
characteristic irregularities in the deposition of calcium salts and in the formation
of narrow cavities in the ossifying cartilage. This sometimes gives rise to marked
ahnormality of form.

In rickets the process of bone absorption is abnormally active, while the
formation of new bone is characterized by lack of deposit of the normal amount
of calcium salts. In endochondral ossification there is no well-marked zone of
calcification. The bones are abnormally thick, clumsy, and heavy and may be
much distorted.

In teratomata of various forms the skeletal abnormalities correspond with
those of the rest of the body.

BIBLIOGRAPHY.

(On general features of the morphogenesis of the human skeleton.)

Aebt, Chr. : Der Bau des menschlichen Korpers. Leipzig 1871.

Arnold, J. : Weitere Beitrage zur Akromegalief rage. Virchow's Arch. Bd. 135,

S. L 1894.
Bach, K. : Zur Physiologie und Pathologie des Thymus. Jahrb. f. Kinderheil-

kunde. Bd. 64. 1906.
Bade, P.: Die Entwicklung des menschlichen Skeletts bis zur Geburt. Arch. f.

mikr. Anat. Bd. 55, S. 245-290. 1900.
Bardeen and Lewis: Development of the Limbs, Bodywall, and Back in Man.

Amer. Joum. of Anat. Vol. 1, p. 1. 1901.
Bardeen, C. R. : Vertebral Variation in the Human Adult and Embryo. Anat. Anz.

Bd. 25, S. 497. 1904.
B^clard : Uber die Osteose oder die Bildung, das Wachstum und die Altersabnahme

der Knochen des Menschen. Meckel's Arch. Bd. 6, S. 405-446. 1820.
Bernats, a.: Die Entwicklungsgeschichte des Kniegelenkes des Menschen mit

Bemerkungen iiber die Gelenke im allegemeinen. Morphol. Jahrb. Bd.

4, S. 403. 1878.
Bolk: Die Segmentaldifferenzierung des menschlichen Rumpfes und seiner Ex-

tremitaten. Beitrage zur Anatomie und Morphologic des menschlichen

Korpers. Morphol. Jahrb. Bd. 27. 1899. Bd. 28. 1899.
Sur la signification de la sympodie au point de vue de I'anatomie segmentals

Petrus Camper Desl 1. 1901.
Bradley, 0. C. : A Contribution to the Development of the Interphalangeal

Sesamoid Bone. Anat. Anz. Bd. 28, S. 528-536. 1906.
Bruch, C. : Beitrage zur Entwicklungsgeschichte des Knochensystems. Neue De;ik-

schriften der allgemeinen SchweizeriseLen Gesellschaft fiir die gesamten

Naturwissenschaften. Bd. 12, S. 16. Zurich 1852.
Corridi, G. : Dei principale nuclei di ossificazione che possono invenirsi alF epoca

della nascita. Uanomalo Napoli. Vol. 3, p. 143, 179, 231. 1891.
de Coulon, W. : Uber Thyreoidea und Hypophysis bei Cretinen, sowie iiber

Thyroichalreste bei struma nodosa. Virchow's Archiv. Bd. 147. 1897.
Damany, p. le: L'adoption de Fhomme a la station debout. Journ. de TAnat.

et de la Physiol, p. 135-170. 1905.
DoRRiEN, Ernst: Uber Riesenwuchs und Elephantiasis congenita. Diss. Leipzig

1905.
Erissonius: Traite des os des enfants. Cited bv I^ Double, 1906.
Grawitz: Fetus mit kretinistischer Wachstumsstoruntr des Sehadels und der

Skelettknoehen. Virchow's Arch. Bd. 100. S. 2-'>6-262. 1885.
Hagen: Die Bildung des Knorpelskeletts bpim men<?^h lichen Embryo. Archiv

f. Anat. und Physiol. Anat. Abt. S. 1-40. 1000.

326 HUMAN EMBRYOLOGY.

Hekke u. Reyher : Studien iiber die Entwicklung der Extremitaten des Menschen,

insbes. der Gelenkflachen. Sitzungsb. der K. Akad. der Wiss. Math.-Naturw.

Klasse. Wien. Bd. 80, S. 217. 1874.
Hepburn, D. : The Development of Diathrodal Joints in Birds and Mammals. Joum.

of Anat. and Physiol. Vol. 23, p. 507. 1889.
HiJTER, Carl: Anatomische Studien an den Extremitatengelenken Neugeborener

und Erwachsener. Virchow's Archiv. Bd. 25, 26, 28. 1862-1863.
Kaupmann, E. : Untersuchungen iiber die sogen. fetale Rachitis. (Chondrodystro-

phia fetalis.) Berlin 1892.
Kerckring, Theod. : Spicilegium anatomicum continens osteogeniam foetuum.

Amstelodami. 1670.
Lambertz: Die Entwicklung des menschlichen Knochengerustes wahrend des fetalen

Lebens dargestellt an Rontgenbildern. Fortschritte auf dem Grebiete der

Rontgenstrahlen. 1. u. 2. Erganzungsheft. 1900.
Launois, p. E., et Roy, Pierre : Des relations qui existent entre T^tat des glandes

genitales males et le developpement du squelette. C. R. Soc. Biol. T. 55.

1903.
LiNDEMANN, P.: Uber Osteogenesis imperfecta. Diss. Berlin 1903.
LuBOSCH, W. : Die Stammesgeschichtliche Entwicklung der Synovialhaut und

der Sehnen mit Hinweisen auf die Entwicklung der Kiefergelenke der

Saugeliere. Biol. Zentralbl. Bd. 28, S. 678, 697. 1908.
LuNDVALL, Havar: Wciteres uber Demonstration embryonaler Skelette. Anat

Anz. Bd. 27. 1905.
Luschka: Die Halbgelenke des menschlichen Korpers. Berlin 1858.
LuNGHETTi, B. : Sopra Possification dei sesamoidi intratendinei. Monit. Zool. Ital.

Anno 17, p. 321-322, 1906.
Mall, F. P. : On Ossification Centers in Human Embryos. The American Joum.

of Anat. Vol. 5. 1906.
Michel, F. : Osteogenesis imperfecta. Virchow's Arch. Bd. 174. 1903.
Morin: Radiographics relatives h la formation et a Taccroissement du syst^me

osseux. Assoc. Frang. pour TAvancem. des Sc. Sess. 27, p. 678-683.

Nantes 1899.
Nobiling: Uber die Entwickelung einzelner Verknocherungskeme in unreifen

und reifen Friichten. Miinchen 1899.
Pfitzner, W.: Morph. Arbeitcn. 1891-1898.
PoNCET, Antonin : De Tinfluence de la castration sur le developpement du

squelette. R^cherches ex perimen tales et cliniques. C. R. Soc. Biol. T. 55.

1903.
Rambaud et Renault: Origine et developpement des Os. Paris 1864.
Regnault, F. : A propos de la morphogenie osseuse. Bull, et Mem. de la Soc.

d'Anthrop, 1907.
Retterer: Ebauche squelettogene des membres et developpement des articulations.

Journ. de TAnat. et de la Physiol. Annee 38, No. 5, p. 473, 580. 1902.
Rosenberg, E.: Uber die Entwicklung der Wirbelsaule und des centrale carpi des

Menschen. Morphol. Jahrbuch. Bd. 1, S. 83. 1876.
Bemerkungen iiber den Modus des Zustandekommens der Regionen an der

Wirbelsaule des Mensclien. Morphol. Jahrbuch. Bd. 36. 1907.
Schubert, C: Riesenwuclis beim Neugeborenen. Monatsschr. f. Geburtsh. u.

Gynakol. Bd. 23, S. 4.53-456. 1906.
ScHULiN, K. : I^ber die Entwicklung und vveitere Ausbildung der Gelenke des

menschlichen Korpers. Arch. f. Anat. u. Phvsiol. Anat. Abth. S. 240-274.

1879.
Schwegel: Die Eutwicklunofs^eschichte der Knochen des Stammes und der

Extremitaten. Sitzb. Akad. Wien. Math. phys. Kl. Bd. 30. 185S.

(Literature.)

MORPHOGENESIS OP THE SKELETAL SYSTEM. 327

SiLBEBSTEiN, A.: Ein Beitrag zur Lehre von den fetalen Knoehenerkrankungen.

Arch. klin. Chir. Bd. 70. 1903.
Thilenius, G. : Untersuchungen iiber die morphologiscbe Bedeutung accessorischer

Elemente am menschlichen Carpus (und Tarsus). Morph. Arbeiten. Bd. 5.

1895.
Accessorische und echte Skelettstiicke. Anat. Anz. Bd. 13. 1897.
Wolff, J. : Uber die Theorie des Knochensehwundes durch vermebrten Druck und

der Knochenanbildung durcb Druckentlastung. Arcb. f. klin. Cbir. Bd. 13,

S. 302 bis 324. 1891.
Wyss, von: Beitrag zur Kenntnis der Entwicklung des Skelettes von Kretinen

und Kretinoiden. Fortschr. auf d. Gebiete der Rontgenstrahlen. Bd. 3. 1900.

B. ORIGIN AND FATE OF THE CHORDA DORSALIS.

The cervical region of the chorda dorsalis appears to arise
from the dorsal wall of the entero vitelline sac beneath the medul-
lary groove, although it is not probable that these cells belong
primitively to the entoderm. In many mammals the tissue from
which it is derived comes primarily from the mesodermal head
or chordal process (see p. 47). Bonnet,^ however, has ascribed to
the yolk entoderm the origin of the tissue for the anterior tip of
the chorda in the dog and sheep, although the main part of the
anterior portion of the chorda in these animals is derived from
tissue which has become incorporated in the entoderm through
fusion of the head process with the dorsal wall of the entero-
vitelline sac. In the human embryo, as mentioned above (p. 293),
there is at a very early period a layer of mesoderm formed
between the ectoderm and entoderm in the mid-sagittal plane
(Fig. 219, A). At a slightly later period (Fig. 219, B and C) the
mesoderm has disappeared in this region. Possibly it is incor-
porated with the entoderm which now beneath the neural groove
presents a plate of tissue slightly thicker than the entoderm on
each side. This is the chordal plate, the anlage of the anterior
end of the chorda dorsalis. Kollmann (1890) has given an account
of the origin of the chorda in a human embryo 2.11 mm. long
with fourteen mesodermic somites. In this embryo (Fig. 220)
the neurenteric canal has disappeared. Anterior to the primitive
streak in the mid-sagittal plane a longitudinal ridge of cells pro-
jects dorsally from the entoderm (Fig. 220, B). This ridge of
cells gradually becomes pinched oflF from the entoderm (Fig.
220, C). In a slightly older embryo described by Mall (1897)
(Fig. 229) the neurenteric canal is represented by a solid column
of cells. The chorda extends forward from this column of cells
as far as the buccopharjoigeal membrane. As Seessel's pocket
develops, the chorda remains for a time attached to its posterior
wall. This connection is lost at about the period when the bucco-
pharyngeal membrane is ruptured.

'Anat. Hefte, 1901.

328 HUMAN EMBRYOLOGY.

In the embryo described by Mall the posterior end of the
chorda lies opposite what is probably the eighth cervical somite.
During the development of the thoracic, lumbar, sacral, and coccy-
geal regions of the embryo the chorda is gradually developed
caudalwards. In this portion of its development the chorda is
not first embedded in the entoderm and then again differentiated
out, but is derived directly from the primitive streak and from
the tissue which replaces the primitive streak caudalwards.

In an embryo described by His (L, 2.4 mm. long) the noto-
chord has a distinct lumen. This is not present in older embryos.

At first there is no distinct membrane about the chorda (see
Figs. 220, B, and 220, C). The cells are large, with clear proto-
plasm. By the end of the fourth week of development a thin
structureless membrane encircles the chorda, which is now about
at the height of its development. The chorda is cylindrical. The
cells are polygonal and are filled with a fine granular protoplasm.
During this period differentiation of the base of the skull and of
the spinal column is marked by condensations in the axial mesen-
chyme (Fig. 231). Subsequently in the spinal region the inter-
vertebral discs and the bodies of the vertebrae form about the
chorda dorsalis. Between the chorda cells and the outer sheath
of the chorda there appears an inner membrane, apparently
mucoid in nature (Williams). According to Minot (1907), at the
period when the axial mesenchyme begins to be differentiated
into vertebras the notochord shows slight transient dorso-ventral
segmental flexures. Just before ossification begins the chorda dis-
appears in the vertebral bodies. In the intervertebral discs it
becomes transformed into the tissue of the nucleus pulposus. In
the cranial region the posterior and the anterior portions of the
chorda dorsalis become embedded in the skeletal tissue of the
base of the skull while the intermediate portion lies between
the base of the skull and the dorsal wall of the pharynx (Fig. 266).
Ultimately the cranial part of the chorda completely disappears.
That part of the chorda which lies in the retropharyngeal tissue
gives rise to numerous projections and swellings and is the first
portion of the chorda to disappear. The posterior portion of the
cranial part of the chorda comes to lie on the dorsal side of the
basal occipital plate and disappears at the time of ossification of
the basi-occipital. The anterior extremity of the chorda persists
longer than the retropharyngeal portion, but usually disappears
during the ossification of the base of the skull. A description of
the changes undergone by the chorda is given in connection with
the development of the vertebral column and skull. Traces of the
cranial part of the chorda dorsalis may persist in the adult and
give rise to tumors.

MORPHOGENESIS OP THE SKELETAL SYSTEM. 329

FiB.230b. Fie- 2300. Eli.230d.

FiQ. 229.— (AttCT Mall, Joliin. of Morpliology. vol. 12. 18»7. Fig. Ifl.) OuUine drawing of ■ mediki
ngitul sectian of (he rnodd of Msll'ii embryo XII. Magn. 50: 1. The heavy line is the aorla. The

Blriated. Am., amnion: a.. Ijorder between fore-brain and mid-brain; X. X'. exwnt of oiofure of gpinal
eonai; 5. BeeBBel'ii pocket; CA., chorda; b'. b'. first and aecood bnmchial poekeU
mouth: T., thyroid; II., pericardial npace: Ph., pharynx; ErU.. ■ ' '

The cvlom within the biMly is represented black. O' and 0>, fint and tl
C, first and eilhth cen-ical myotomes; T, tint thoracic myotome; a., aoi
I., thyroid; l- liver: Ph.. pharynx; i., intestiae; ne.. neurent^ric canal: A

330 HUMAN EMBRYOLOGY.

ENTOCHOBDA.

A hypochorda or entochorda arising fitwn the entoderm beneath the chorda
dorsalis has been found in fishes, amphibia, birds, and reptiles, but apparently
has not yet been described for the human embryo. In part the tissue of the
hypochorda joins that of the chorda dorsalis. (See Ad. Reinhardt, Morphol.
Jahrb., Bd. 32, 1904; Ph. Stohr, Morphol. Jahrb., Bd. 23, 1895; and S. A
Ussoff, Anat. Anz., Bd. 29, 1906.)

BIBLIOGRAPHY.

The chief paper on the early development of the chorda dorsalis in man
is that of Kollmann (1890). Important data concerning the chorda dorsalis are
to be found in the various papers deseribmg human embryos with fourteen
somites or less.

Bonnet : Beitrage zur Embryologie des Hundes. Anat. Hef te. 1897 und 1901.
Eternod: Conununication sur im oeuf humain avec embryou excessivement jeune.
Arch. Ital. de Biologies Vol. 22. 1895. See also Monitore Zool. Ital.

Vol. 5, p. 70-72. 1894.
Sur un OBuf humain de 16,3 muL avec embryon de 2.1 mm. Arch, des Sciences

Phys. et Nat. Ann6e 101. 4 Periode. T. 2, p. 609-624. 1896.
H y a un canal notochordal dans Tembryon humain? Anat. Anz. Bd, 16,

p. 131-143. 1899.
Frassi, L. : Uber ein junges menschliches Ei in situ. Arch, f . mikr. Anat. Bd. 71,

S. 667. 190a
Froriep, a. : Kopfteil der chorda dorsalis bei menschlichen Embryonen. Beitrage

z. Anat. und Embryol. Als Festgabe fUr Jacob Henle. 1882.
GiacX)minIt C. : Un CBuf humain de 11 jours. Arch. Ital. de Biologic. Vol. 29.

1898.
Heiberq, J.: Uber die Zwischenwirbelgelenke und Knochenkeme der Wirbelsaule.

Mitt, a, d. Embryol. Inst, der K. K. Univ. Wien. I, S. 119-129. 1880.
His: Anatomic menschlicher Embryonen. 1880.
Janosik, J.: Zwei junge menschliche Embryonen. Arch. f. mikr. Anat. Bd. 30,

S. 559. 1887.
Keibel : Zur Entwicklungsgeschichte der chorda bei Saugem. Arch, f . Anat. und

Physiol. Anat. Abt. 1889.
Kollmann: Die Entwicklung der chorda dorsalis beim Menschen. Anat. Anz.

Bd. 5, S. 308-321. 1890.
Die Rumpfsegmente menschlicher Embryonen von 13-35 Urwirbeln. Arch.

f. Anat. u. Physiol. Anat. Abt. 1891.
Leboucq, H. : Recherches sur le mode de dispnrition de la chorde dorsale chez

les vertebres sup^rieurs. Arch, de Biol., p. 718-736. 1880.
Luschka: Die Halbgelenke, 1852; 2. Aufl. 1858.

Die Altersveranderung der Zwischenwirbelknorpel. Virchow's Arehiv. Bd. 9,

S. 309-327. 1856.
Uber gallertartige Auswiiclise am Clivus Blumenbachii. Virchow's Arehiv.

Bd. 11, S. 8-12. ia57.
Mall: A Human Embryo 26 Days old. Joum. of Morph. Vol. 5, p. 459-480. 1891.

Human Ccelom. Joum. of Morph. 1.S97.
MiNOT, C. S.: The Segmental Flexures of the Notochord. Anatomical Record,

Amer. Joum. of Anat. Vol. 6. 1907.
MuLLER, H.: Uber das Voikomnien von Resten der chorda dorsalis bei Menschen

nach der Geburt. Zeitschrift f. rationelle Med. Bd. 2. 1858.
MusGRAVE, James : Persistence of the Notochord in the Human Subject. Joum. of

Anat. and Physiol. Vol. 25. 1891.

MORPHOGENESIS OP THE SKELETAL SYSTEM. 331

Robin, C. : Memoire sur revolution de la notoeorde. Paris, 212 pp., 1868.
RoMiTi, G. : Rigonfiamenti della corda dorsale nella porzione cervicale nelFembrione

umano. Notizie Anat. Siena. 1886.
Spee, Graf v.: Beobachtungen an einer menschlicben Keimscheibe mit offener

Medullarrinne. Arcb. f. Anat. und Pbys. Anat. Abt. S. 159-176. 1889.
Neue Beobachtungen iiber sebr friihe Entwicklungsstufen des menschlicben

Eies. Arch. f. Anat. und Pbys. Anat. Abt. S. 1-30. 1896.

On the development of the notochord in the higher mammals see especially:

Williams, L. W. : The Later Development of the Notochord in Manmials. Amer.
Jour, of Anat. Vol. 8, p. 251. 1908.

C. VERTEBRAL COLUMN AND THORAX.

The development of the vertebral column and thorax may be
divided into three overlapping periods : a membranous or blaste-
mal, a chondrogenous, and an osteogenous.

The Blastemal Pebiod.

The division of the axial mesenchyme into segments, sclero-
tomes, which correspond to the myotomes and spinal ganglia, is
marked at an early stage by intersegmental arteries (Fig. 233,
A. is.). The segmental differentiation extends into the region
dorsal to the spinal cord, but ventrally it does not reach the chorda
dorsalis. Each sclerotome becomes divided into two portions, a
caudal half in which the tissue is condensed, and a cranial half in
which the tissue is less dense (Fig. 234). In sections through
hardened tissue a slight fissure, the intersegmental fissure (v.
Ebner, 1888), may partially separate the two halves.®

From the condensed tissue of the caudal half there arises a
primitive vertebra of Remak, or scleromere, with dorsal (neural)
and ventral (costal) processes and chordal processes which unite
these to the perichordal sheath, a dense layer of tissue forming a
continuous sheath about the chorda dorsalis (Figs. 234, 237, 238,
240, 241, 242). From the tissue of the anterior halves of the
sclerotomes arise * * interdorsal membranes" which unite the dorsal
processes of the scleromeres (M. id., Figs. 236, 244, 245, 247), and
*-interventral membranes" which unite the bases of the ventral
processes {M. ii\, Figs. 235, 243, 244, 245). The chordal processes
become hollowed out caudalwards by a loosening up of their tissue
and strengthened cranialwards by a condensation of tissue imme-
diately bounding the intervertebral fissure (Figs. 234, 235, 243,

* Schultze (1896) has described in a correspondine: position in selachians
and reptiles a diverticulum which communicates with the myocoel. The fissure is
apparently to be looked upon as an offshoot of the myocoel. In birds the
fissure is said to arise independently of and to fuse secondarily with the myocoel.
In mammals it appears after the myotome has become independent and the
myocoel has disappeared.

332

HUMAN EMBRYOLOGY.

Fxa. 231.

Fio. 232.

Fios. 231 and 232. — Diagrammatic outlines to represent the development of the skdetoo during
the blastemal period.

Fig. 231. Embryo II, length 7.5 mm. Fig. 232. Embryo CIX, length 11 mm. o, occipital; c», first
cervical; 0, first thoracic; i*. first lumbar; »', first sacral; co^, first coccygeal vertebra.

MOKPHOGEXESIS OP THE SKELETAL SYSTEM.

Njp.

47^:

mbryo.

3 LXXX. length 5 n

engtri 3.S mn). Pig. 234. Eir
335 and 236. Embryo CCXl.I. Isnglh 6 mm. Fi(. 235 throu(li th(
23S through b more dons) plane. Fig*. 233. 236. 238 repre«nt iwcdons cut somewhat obliquely so that
(h« right Bide of ihB Miction. » ventraJ to the left. In Fig». 234 and 236 on the right side the bodie. of
several embryonic vertebne are reprewnled in outline. In Figa. 234 and 235, owing to artefncli, the
myotomes ore pulled away from the iwlerolometi. ..4.i«., arteria interugmentalia; Cntt., ctelom; Chjl.,
chorda domlui; Der., dermis; F.v.E.. fissure of v. Ebner (intenertebntl Huure); M.id., membrans
interdoTvalis; Af.tc.. membiaLimiiiteTventralia; M.ip.. spinal cord; Myo.. aiyatome: ^.fp.. nervua »pina-
lia; PiAS., perichontal nheath; Pr.c. proeewuj eoslalis; PrjA., proM9»u« chord»li>; Pr.n.. proee8.«uB
Dcuralis; Stl„ sclerotome; V^., vena cardioaLifl.

334 HUMAN EMBRYOLOGY.

244, 245). There is thus formed about the intervertebral fissure
a primitive intervertebral disc.® The tissue lying between each
two discs now becomes completely surrounded by a membrane of
condensed tissue, which may be termed an interdiscal membrane
(Fig. 246, M. iv.). Meanwhile the perichordal sheath between
each two discs becomes extended ventrodorsal) y, so that it gives
rise to a *' perichordal' ' septum which divides into two parts the
space surrounded by the interdiscal membrane (Figs. 239, 246,
247, Pch.s.).

During the earlier stages of the blastemal period the sclero-
meres are essentially similar throughout the length of the ver-
tebral column. The differentiation of the scleromeres begins in
the cervical region and extends caudalwards. At the end of the
first month of development the scleromeres present the appearance
shown in Figs. 231, 240, 241, and 242, although their margins are
less sharply marked than it is necessary to represent them in the
model. At this period of development the interdorsal and inter-
ventral membranes have begun to appear in the cervical region,
but are not represented in Fig. 231. Soon after this period the
thoracic region of the spinal column becomes distinguishable from
the neighboring regions through the great development of the
costal process of the thoracic scleromeres (Figs. 232 and 239).
Meanwhile centres of chondrification arise. These are described
below. ^^

The Occipital Region. — In man, as pointed out above, the
primitive axial mesenchjone in the head posterior to the otic
region undergoes a partial segmentation. At the end of the first
month of development there are three fairly well-marked occipital
myotomes which afterwards disappear. The axial mesenchyme
corresponding to these myotomes is not definitely divided into
sclerotomes, although that opposite the last occipital myotome
becomes divided like each of tiie spinal sclerotomes into a light

•I have elsewhere (1905) called the united chordal processes of the
scleromere a primitive intervertebral disc, but it seems better to restrict this term
to the structure here described. According to Williams the primitive intervertebral
discs are to be regarded as places in which the tissue remains dense while between
them the differentiation of the bodies of the vertebras is marked by a loosening
up of the tissue. According to Williams the scleromeres are not true morphological

imits.

*** Charlotte Miiller (1906) has described a transitory, longitudinal ridge of
cells which extends between the mid-ventral surface of the spinal column and
the aorta. Opposite the primitive discs this ridge is connected to the anlages
of the corresponding ribs by bands of tissue (hypochordal Spangen) which are
not fused to the discs. Opposite the vertebral bodies the lighter tissue of the
bodies is continued into the lighter tissue of the centre of the ridge of cells. The
ridge extended from the second to the ninth thoracic vertebra in a 13 mm.
embrvo. There is no segmentation visible in the tissue of the ridge.

MOEPHOHEN'ESIS OF THE SKELETAL SYSTEM.

1

Pr

riOB. 237

-23a.— (.\fter

Bsideen. At

of Anal..

vol.

W. lOOa.) Croi*.»«!tion.

! through

lidthoradc Ha

nentK during

the blutema

1 pilriod of v.

srtebral de

velo

53:1.

Hg. 237.

Embryo LXXVI. Iwfth

4.5 mm. The right e

ide .

TT, ^^'

liddls. the led

: aide through

e fifth Mgmer

Imbryo II,

lecEth 7

,m. Fifth tht

inoic Mmoent.

, The right

Eide of the di

■BKiag rep

terior to lY.

; the left. Fig. 239. Embry

o CI.XXV. 1<

math 13 ram.

The left

hall

of theeixthvei

rl«b™l boc

detail ; the body-wall. «pii

na] oord, .

Qd-

pioal g.r.gbon .

re <hown i

n outline.

J., region of

riee;

C.r.. corpus v.

Brtebnp; Co«o, rib:

hj.. chords d

ar»l>>; Due. i

intervert«br»l diM; Gjp..

g.»gl. -pi

oale

: *f.d., dor«lr

nuaculatur

e; M^..

.edulli apiaali

«: Mva.. myotome; Njp.

. neryu. .pi.

laJi^ Pr.<

rocessus coelalii

«; Pr^.,

anterior and a condensed posterior half (scleromere). The lighter
half is continuous apicalwards with the slightly condensed, unseg-
mented mesenchyme which lies in the region of the more anterior
occipital myotomes. This in turn Is continued into a thin layer of

HUMAX EMBRYOLOGY.

FtQ. Z4C.
— (Afwr Banleen, i

FlQ. 247.

FiGB. 2«-247.— (Afwr Banleen, Ainer, Joum. of Anftt., vol. Lv, 1905.) \ie»a of modcla repre-

Fig9. 240-242. F.mbryo tl. length 7 mm. Ma(a.33):l. FiO- 243-245. Embn'O CLXIII, length 0
. Magn. 23 ; 1. Figs. 246, 247. Embryo CIX, lengtli 11 mm. Magn. 2S : 1. Figa. 240. 243. 246.
n from in front: Figi. 241, 244. 247. views from the nde: Figs. 242, 24S, \iewt! from briiind. A.U..
'rii Inter^menlsUx: CA.(f.. rhiHila dorealis; Diar, mtervert«biAldi«: M.iif., manbrsasiDlenloraalia;

I'd

MORPHOGENESIS OF THE SKELETAL SYSTEM. 337

dense tissue which is closely applied to the back of the pharynx.
The chorda dorsalis surrounded by a perichordal sheath is con-
tinued from the spinal region through the centre of the occipital
sclerotome and the tissue in front of this into the dense tissue on
the back of the pharynx, in which it may be followed to Seessel's
pocket. Fig. 231 represents the sclerogenous tissue of the occipi-
tal region at the end of the first month. The posterior portion
of this, corresponding in form with the first cervical scleromere,
is composed of very dense tissue. Anterior to this the tissue is
much looser in texture. The occipital scleromere has fairly well
developed neural and chordal but has no clearly marked costal
processes. No clearly defined interdorsal and interventral mem-
branes are developed from the light half of the first cervical sclero-
tome. For the subsequent changes which take place in this region
see p. 343.

Chondbogenous Period.

On each side of the blastemal vertebra three primary centres
of chondrification appear at about the same time, one for the
neural process, one for the costal process, and one for the verte-
bral body. Fig. 239 shows these centres as they appear in a cross
section at an early period. Figs. 248 and 249 show, the early car-
tilages of an embryo slightly older (length 14 nma., age five and a
half weeks).

The cartilages of the vertebral body are formed by a trans-
formation of the loose tissue lying between the primitive inter-
vertebral discs and surrounded by the interdiscal membrane. At
first the cartilage of the left side is separated from that of the
right by the perichordal septum. Soon this is broken through and
the two cartilaginous anlages of the vertebral body become united
about the chorda. In the thoracic region this union seems to take
place at about the same time dorsally that it does ventrally. A
sagittal section through the thoracic region of an embryo at this
stage is shown in Fig. 250. The chorda dorsalis is surrounded by
a perichordal sheath. The latter is encircled by dense inter-
vertebral discs which alternate with light cartilaginous bodies,
surrounded by perichondrium which is less condensed than the
tissue of the discs. Ventrally and dorsally longitudinal ligaments
have been differentiated from the surrounding mesenchyme.

According to Schultze (1896), the cartilages of the bodies
lengthen at the expense of the discs and finally fuse to form for a
brief period a continuous cartilaginous colunm. In human em-
bryos between 20 and 40 mm. in length the discs become very thin
near the chorda dorsalis, but the centre of the disc does not become
so completely differentiated into embryonic cartilage that it is
not possible to distinguish the boundaries between successive ver-

Vou I— 22

HUMAN EMBRYOLOGY.

i

Fla. 26S. Flo. 256.

Fio. 257. Fio. 258. Fio. 259.

FioB. 248-269.— (After flardeen. Anier. Journ. of Anal,, vol. iv. 1B05.)

FigB. 248. Z4B, 251, 252, 254. 255, 257, 258. Ventral, lateral, and doraal views of inodelj' made by

vertebne during the chandrogenoui" period. On the left fjde the cartllaginouii, on the right the envelop-
ing fibrous liwue i* shown. The latter is also shown on the eighth vertebra in Fig. 252. Fign. 248. 249.
Embrj'o CXI.IV, lengtli 14 mm. M«gn. 17 : 1. Figs. 2.11. 252. Embryo XXII. length 20 mm. Magn.
13:1. Figs. 254. 255. Embryo CXLV. length 33 mm. Magn.QM. Figs. 2S7, 258. Embryo LXXXIV,
lengtliSOmm. Magn. 9:1. Fig. 257. dorsal view, left half . Fig. 258. median view.

Figs. 250, 253, 250. 259. flagittal -enions in the mid-line through the niilh, seventh, and eighth
thoracic segments of a series of embr>-oi! from 15 lo 50 mm. long. Fig. 250. Embryo CXLI\'. length
14 mm. Fig. 25B. Embryo C\'1I1, length 22 mm. Fig. 256. Embryo LXXIX. lenglh 33 mm. Fig. 259.
EmbryoCLXXXlV.lengIh50mm, C.e.. eorpus vertebra; Co«o, rib; CA.rf., chorda dorsalis; Z>t«, inteiw
vertebtaldise; I,., lamina; L.v.. lig. ventrale; /'r.a.a.. proc.articulariaant. Isup,); Prji.p., proe. articularia
post. {iaf.J; Pr.n.. proc. neumlis; Fr.rd., prae. radicularit; Pr.t.. prnc. spinaliK; PrJr., proc. transvecBus.

MORPHOGENESIS OP THE SKELETAL SYSTEM. 339

tebral bodies. According to Charlotte Miiller (1906), the inter-
vertebral tissue near the chorda so far undergoes chondrification
that capsules may be seen about the tissue cells. This stage is
quite transitory. At the periphery of the discs the annulus fibro-
sus is meanwhile differentiated more and more into a condition
resembling the adult (Figs. 250, 253, 256, 259).

The chorda dorsalis at the period shown in Fig. 250 is of about
the same size at the level of the discs as at the centres of the
bodies. It may become slightly swollen in the bodies, but as the
bodies increase in size at the expense of the discs the chordal
canal becomes enlarged in the intervertebral areas and constricted
at the centres of the bodies (Figs. 253, 256, and 259). The chorda
loses its continuity and the chordal cells become clumped in the
vicinity of the discs, spread out there in the form of a flat disc
(Fig. 258), increase in number, and give rise to the nucleus pulpo-
sus. Meanwhile the chorda cells lose their cell membranes and
form a syncytium similar to that of the mesenchyme. About the
cells mucin is formed in considerable amounts (Williams). The
chordal canal long remains in the vertebral body (Figs. 256 and
259). The chordal sheath remains in the canal until the period
of ossification.

The cartilage of the bodies in embryos of the sixth week
(Figs. 248, 249, and 250) is of an early, embryonic, hyaline type.
At a slightly later stage (Fig. 253) two regions may be distin-
guished, a central and a peripheral. The peripheral cartilage
resembles that of the preceding stage, while the central cartilage
is more dense. Gradually the cartilage at the centre of the body
undergoes further changes. The cells enlarge and become sharply
set off against the matrix, and finally an invasion of vascular tissue
takes place, chiefly from the posterior surface. These changes in
the cartilage are preliminary to ossification.

During the development of the vertebral bodies changes have
been active in the neural processes. At the period represented in
Fig. 239 the neural cartilage is a small, flat body situated in the
dorsal process of the blastemal scleromere; from this as a centre,
radicular, transverse, cranial (superior) and caudal (inferior)
articular, and laminar processes are rapidly developed. This
structural differentiation may be followed in Figs. 248, 249, 251,
252, 254, 255, 257, 258.

The cartilaginous radicular processes are at first slender rods
which grow out towards and finally fuse with the corresponding
vertebral bodies (Figs. 249 and 251). Froriep (1883) has shown
that in the chick these processes form a more essential element
of the body than in mammals. In the atlas they form a part of the
ventral arch, but in the thoracic region of mammals they fuse with
the posterolateral portion of the corresponding vertebral bodies.

340 HUMAN EMBRYOLOGY.

After their junction with these the radices of the arches increase
in size but otherwise show no marked alterations of form.

The transverse processes are at first short projections which
lie at some distance from the corresponding ribs (Fig. 249). At
the time tubercles are developed on the ribs the transverse proc-
esses grow outward and forward to meet them (Figs. 252 and
255). At first the developing cartilage of each rib and the cor-
responding vertebral transverse process are embedded in a con-
tinuous blastema, but before chondrification has proceeded far
branches from successive intervertebral arteries become anasto-
mosed in the region between the neck of the rib and the transverse
process. Fig. 239, Aa, shows the loose tissue through which this
arterial anastomosis will take place.

Between the extremity of the cartilaginous transverse process
and the rib a joint cavity is developed, and the surrounding blas-
tema is converted into the joint capsule and the costo-transverse
ligaments. Similarly a joint is developed between the head of
the rib and the corresponding intervertebral disc and vertebral
bodies.

The articular processes develop slowly from the cartilage
(Figs. 249, 252, and 255). Extension takes place anteriorly (Pr. a a.)
and caudalwards {Pr. a.p.) in the interdorsal membranes. In an
embryo of 14 mm. (Fig. 249) these cartilaginous articular plates
are separated by a distinct interval. In one of 17 mm. they have
approached each other very closely ; and in one of 20 mm. not only
do the articular processes show distinctly more form (Fig. 252),
but in addition the inferior articular process of one vertebra
slightly overlaps the superior process of the vertebra next pos-
terior. This overlapping of the articular processes is distinctly
more advanced in an embryo of 28 mm. and still more so in one
of 33 mm. (Fig. 257). In a fetus of 50 mm. (Fig. 258) conditions
essentially like the adult have been reached.

The laminar processes scarcely exist in an embryo 14 mm.
long (Fig. 249). In an embryo 20 mm. long (Fig. 252) they have
begun to project dorsal to the region of the articular processes.
The dense embryonic connective tissue covering the laminar
processes at this stage gives attachment to a membrane surround-
ing the spinal cord, membrana reuniens dorsalis, and to another
one covering the dorsal musculature. In a fetus of 33 mm. the
laminar processes extend well toward the mid-dorsal line (Fig.
255) ; in one of 50 mm. (Figs. 257 and 258) they completely en-
circle the spinal canal and from the region of fusion of each pair of
laminar processes a spinous process extends distally, though not
so far as in the adult. The completion of the spinal canal takes
place earlier in the thoracic than in the cervical and lumbar
regions.

MORPHOGENESIS OP THE SKELETAL SYSTEM. 341

Alterations in the cartilage of the neural processes prelim-
inary to ossification begin at about the time that they take place
in the vertebral bodies. They are first seen in centres which cor-
respond to those in which the neural cartilage begins in the blas-
temal neural processes. In a fetus of 50 mm. calcification may be
seen in the arches of the first cervical to the sixth thoracic ver-
tebrae.

From the blastemal tissue surrounding the cartilaginous ver-
tebrae are developed the various ligaments of the spinal column.

Summary. — Each cartilaginous vertebra is developed from
four centres of chondrification. In addition a separate centre
appears for each rib. In comparing these centres with the blas-
temal formative centres, we find that each primitive centre of
blastemal condensation enters into union with tissue derived from
the anterior half of the body-segment next posterior and then gives
rise to three centres of chondrification, one for the neural arch,
one for the rib, and one for a lateral half of a vertebral body.
When ossification first takes place the centres of ossification of
the neural arches and the ribs correspond to the original chon-
drification centres in the blastema, but the centres of ossification
of the bodies in most of the vertebrae show little trace of the
bilateral origin of the centres of chondrification.

REGIONAL DIFFERENTIATION.
THE THORACIC VERTEBRiE AND THE THORAX.

The chief steps in the development of the thoracic vertebrae
have been described in the preceding section. In the blastemal
stage these vertebrae became differentiated from the cervical and
lumbar by the greater development of the thoracic costal processes.
During the chondrogenous stage this difference becomes still more
marked. The distal ends of the thoracic costal processes grow
rapidly forward (Figs. 260 and 261). The cartilaginous ribs which
are differentiated in these blastemal processes do not fuse with
the vertebrae, but are connected with them at first by dense tissue
and later by joints and ligaments. The blastemal distal ends of
the ribs at first take a nearly horizontal direction (Fig. 260),
but later their course of development becomes altered by the
heart and liver. (See Figs. 261-263.) The distal blastemal ends
of the ribs become united by a blastemal tissue to form on each
side a sternal plate (Fig. 261). This sternal plate proximally is
fused with the anlage of the clavicle and distally extends to the
blastema of the seventh rib. The fusion of the tips of the more
distal true ribs into the sternal plate does not always take place in
regular sequence. The eighth rib is connected near the sternal
aniage with the blastema of the seventh and the ninth with that of

342 HUMAN EMBRYOLOGY.

the eighth rib. Tlie tenth rib becomes similarly attached to the
ninth. The attachment of eaoh of the three distal ribs to the one
next anterior is apical up to the latter half of the second month.
After this it is marginal (Ch. Miiller, 1906).

Fig. 262. Fia. 263.

FiOB, 260-303.— (After Charlotte Holler, Morpholos. Jihrb.. 1906.) The developmeat of the nrti-

Fig. 260. Embryo 13 mm. long. Fig. 261. Embryo 17 mm. long. Fig. 262. Embryo 16 mm. looc.
fig. 263. Embryo 32 mm. long.

The sternal ends of the clavicles become united with one
another by a dense band of tissue which probably represents the
episternum of lower forms (Fig. 261). Later, when the heart has
descended into the tlioracic cavity, the cranial ends of the sternal
plates become united with one another, and the epistemal band
becomes united to them and loses its intimate connection with the
clavicles (Fig. 262). It normally disappears before the end of the
second month. The sternal bands gradually become fused through-

MORPHOGENESIS OF THE SKELETAL SYSTEM. 343

out their length to form the sternal anlage (Fig. 263). Sometimes
fusion takes place distally before it is completed in the middle.
The ensiform process is formed by the fusion of bands of tissue
which extend distally from each sternal plate. The eighth pair
of ribs does not enter into its formation (Ch. MuUer). Chondri-
fication takes place in the sternal plates at the time these begin
to fuse to form the unpaired sternum. According to Ch. Miiller,
chondrification extends from the ends of the ribs into the sternal
anlage, and the separation of the cartilaginous ribs from the
sternum is a secondary process. The order of separation is not
always regular. Some investigators assume that special centres
of chondrification arise in the sternum.

LITERATURE.

The most important papers on the early development of the human stemmn
are those of G. Ruge, Morphol. Jahrbuch, Bd. 6, 1880; A. M. Paterson, Joum.
of Anat. and Physiol., Vol. 35, 1901; and Ch. Muller, Morphol. Jahrb., 1906.
Not infrequently the epistemal rudiments, instead of fusing completely with the
sternum, become ossified either as separate bones or as bony projections from
the upper margin of the sternum. (H. Eggeling, Verb. Anat. Gesellsch., 1903.)
Paterson describes a sternal anlage independent of the ribs. The existence of
such an anlage is disputed by Ch. Muller. Krawetz (1905) describes in the
mouse two sternal anlages which have an origin independent of the ribs.

CERVICAL, VERTEBRE AND THE BASE OF THE OCCIPITAL BONE.

During the earlier stages of development the cervical vertebrae
resemble those of the thoracic region. The two regions soon
become differentiated from one another bv the much greater
development of the costal processes in the thoracic region (Fig.
232). The seventh cervical vertebra alone, as a rule, has large
costal processes and these do not extend far beyond the transverse
processes of the neural arches.

In the costal processes of the seventh cervical vertebra centres
of chondrification are found at the period when similar centres
appear in the ribs. Centres of chondrification in the rest of the^
cervical vertebrae appear much later, usually not until the embryo
has reached a length of from 16 to 18 mm. According to Valenti
(1906), there are normally no separate centres of chondrification
in the costal elements of the cervical vertebrae, but chondrification
extends into them from the cartilage of the bodies. There seems,
however, good evidence of separate costal centres which arise near
and quickly fuse with those of the bodies.

As in the thoracic vertebrae, there are two bilaterally placed
centres of chondrification for each of the vertebral bodies. These
soon fuse with one another ventral and dorsal to the chorda dor-
salis. Tn the first two vertebrae the ventral fusion takes place
before the dorsal fusion.

344 HUMAN EMBRYOLOGY.

Tliere are separate centres of chondrification for the neural
processes. In the more caudally situated cervical vertebne these
centres are similar to those of the thoracic vertebrje. In the
more cranially situated cervical vertebra? each neural centre of
chondrification appears as a basal plate lateral to the cranial end
of the body of the vertebra. With this it soon fuses. From this

post

Cho

Fio. iOS.

o{ the cervinl vertabifE and theoccipiulcftrtilace of ■» embryo

plate-like base chondrification extends rapidly into the main part
of the arch. From the neural arches are developed laminar, artic-
ular, and transverse processes. The cartilaginous costal centres
become fused medially with the bodies of the vertebrae and laterally
with the tips of the transverse processes. The dorsal growth of
the laminar processes and the formation of the spinous processes
of the cervical vertebrie take place in the main as in the thoracic.
When fully formed, however, the cartilaginous cervical vertebrse

MORPHOGENESIS OF THE SKELETAL SYSTEM. 345

have essentially the shape of the adult osseous cervical vertebrae.
Even before the end of the second month of development distinct
cervical characters may be distinguished.

Specific mention must be made of the mode of development of
the epistropheus, of the atlas, and of the basioccipital.

Epistropheus. — The general mode of development of the epi-
stropheus is like that of the other cervical vertebras. The dens
represents the body of the first cervical vertebra. Union of the
body of the first vertebra with that of the second takes place
through the transformation of the intervertebral disc into hyaline
cartilage, first lateral to the mid- sagittal plane, then later in this
plane. Fig. 265 represents a stage where the lateral fusion is
complete while the medial fusion has not yet taken place. The
articulations between the superior articular processes of the epi-
stropheus and the lateral masses of the atlas apparently are
developed rather in the interventral membranes than in the inter-
dorsal membranes. (See Fig. 264; compare with Figs. 249, 252,
255, 258.)

Atlas (Figs. 264 and 265). — The base (radicular process) of
each cartilaginous arch piece of the atlas becomes temporarily
fused with the cartilage of the body (14 mm. embryo). This fusion
is brought about by incompletely differentiated cartilage, and
soon after it takes place the precartilaginous tissue between the
arch and the body becomes transformed into a dense blastemal
tissue in which ligaments and a joint cavity are later developed.

Meanwhile, during the period of chondrification in the arches
and bodies of the cervical vertebrae, there takes place a condensa-
tion of tissue on the ventral margin of each of the more proximal
cervical intervertebral discs near the cranial end of the vertebral
body which lies caudalwards from it (Fig. 266). These condensed
transverse bands of tissue connect the ventral ends of the blastemal
neural processes with one another. They represent the hypo-
chordal Spangen or braces of Froriep, and may appropriately be
called hypochordal arches. In their intimate relations to the inter-
vertebral discs they apparently differ from the hypochordal
Spangen described by Charlotte Miiller in the thoracic region of
the human embryo (see note, p. 334). In man the hypochordal
arches are transitory in all except the first cervical segment. In
the more distal segments the tissue composing them seems to
become merged in the intervertebral discs without going beyond
the blastemal stage. In the first cervical segment the hypochordal
arch becomes chondrified at the time of the separation of the
arches from the body after the temporary fusion mentioned above.
The cartilage of the hypochordal arch becomes united on each side
to that of the neural hemiarch. There are evidences of two bilat-
erally placed centres of chondrification in the hypochordal arch.

346 HUMAN EMBRYOLOGY.

but fusion of these centres with one another and with the cartilage
of the neural hemiarches takes place as soon as ehondrification is
well under way. According to Froriep (1883), in the cow there
is a single median centre in the hypochordal arch. In the white
rat, according to Weiss, there are two bilaterally placed centres of
ehondrification in the hypochordal arch of the atlas. Froriep
reports in the cow temporary centres of ehondrification in the other
cervical hypochordal arches, but no true cartilage formed, except

Stpl.niui
Fia. 266.— Sa^tUl sectian throush the hud or an embryo 14 mm. Ions. Arcui AvpaA-. ■rcua
hypoehordsliB, bypochordiJ bi»c« or "Spatige"; A, 6o«(., arteri* bluularis; Calv. mrmbr., a^vKi* Btan-
brsnMeft; Cart, occ.. oartilBgooocipitaliB; Cart. «pft.. cartilage iphenoidalii; C i. fl, corpus vertfbiw sextK;
CA. rf., thorda doraaliB: Lintr., Uogua; (Ewp*., aaophagus; Si^ii. noji. »«ptum nam; Tr., trache*.

very temporarily in that of the epistropheus. Weiss found no
ehondrification in any hypochordal arch in the white rat except
that of the atlas."

According to Sehauinsland (Hertwig's Handbuch, 1906), the neural arches
of the mammalian vertebne contain elements of both the ventral and dorsal arches
found in the lower vertebrates, and the ribs belong primitively to the ventral
arches. In the mammals and man, however, the presence of ventral arch elements
is manifest merely in the caudal and cen-ical regions. In the caudal region
temporary hsemal processes are developed (see p. 352). In the cervical region the
ventral arches are refiresented by the hypochordal braces or arches. In reptiles
and birds the hypochordal arches are more extensively developed than in man.

"Ganfini (ISWO) has reported in a number of eases the apparent rudiments
a hypochordal arch in connection with the basilar portion of the occipital.

MORPHOGENESIS OP THE SKELETAL SYSTEM. 347

The costal processes of the atlas become fused medially to the
basilar part of the neural arches {Fig. 264).

For a brief period (14 mm. embryo) the bases of the neural
arches of the atlas and epistropheus together with the tissue inter-
vening between the atlas and occipital bone become fused into a
nearly continuous mass of precartilage {Fig. 267).'*

Basioccipital. — It has already been pointed out that opposite
the last occipital myotome the axial mesenchj-me is differentiated,
like that of the spinal sclerotomes, into a light anterior half and a
dense posterior half. Tlie dense posterior half is called a sclero-
mere. In the spinal region each scleromere joins with the
light half of the sclerotome next posterior in giving rise to the
body and arch processes of
a spinal vertebra. In man
the occipital scleromere is
not thus associated with the
light half of the first spinal
sclerotome. On the con-
trary, it becomes associated
with the lighter tissue of its
own segment and with the
tissue into which this is con-
tinued cranialwards. Fi:?.
266 may serve to illustrate F'o- ae:.— sagittai >»iion through the uieni p>rt

,1' Ti -111 Jill J of the cervical rapan of theepioal coJiuna of the embryo

this. It will be noted that .bown in Fi(. zee.

the anterior half of the first

spinal sclerotome is composed of light mesenchjTnatous tissue,

while the basioecipital and the bodies of the spinal vertebrse are

composed of cartilage.

Chondrification of the base of the occipital begins in two
bilaterally situated centres in the posterior portion of the occipital
anlage. The union of these centres takes place caudalwards
ventral to the notochord and apiealwards dorsal to the notochord.
The neural processes of the caudal part of the occipital anlage
seem to have separate centres of chondrification, but these centres
fuse almost immediately with the centres of chondrification of the

"Hagen (1900) gi\-es a aomewhal different account of the development of
the atlsB and epistropheus in man. He concludes (1) that the dens epistrophei
arisea from the region of the body of the epistropheus and a portion of the
body of the atlas, (2) that the massie laterales of the definitave atlas arise from
the rest of the primary anlag« of the body of tlie atlas, and (3) that the short
piece which luiites them in front arises from the fusion of both neighboring
septa. According to Weiss (1901), the liglit, cranial half of the first spinal
sclerotome gives origin to a cartilaginous tip on the dens epistrophei. The caudal
part of the occipital Weiss r^ards as arising from the neural processes of the
last occipital scleromere. Robin (1864) gives several good pictures of early
stages of the cartilaginous cervical i.'ertebrTE.

348 HUMAN EMBRYOLOGY.

body. Figs. 264 and 265 show the appearance of the occipital
cartilage toward the end of the second month of embryonic devel-
opment. For further details see the subsection on the develop-
ment of the skull.

Ligaments and Joints. — The atlanto-occipital like the lateral
atlanto-epistropheal diarthroses are apparently formed rather in
the interventral than in the interdorsal primitive membranes.
From the interdorsal membranes between the atlas and the occipi-
tal bone arises the membrana atlanto-occipitalis.

From the periphery of the perichordal part of the light ante-
rior half of the first spinal sclerotome are differentiated the cranial
extremities of the anterior and posterior longitudinal ligaments,
of the tectorial membrane, and of the alar and the crucial liga-
ments of the atlas. About the chorda dorsalis in this region the
lig. apicis dentis is differentiated, probably chiefly from the peri-
chordal tissue.

Cartilaginous and osseous nodules found occasionally in this
ligament have been thought by some to represent remnants of
the original tissue of the chorda (H. Miiller, 1858). Albrecht
(1880) advanced the view that these nodules represent the vestige
of a supplementary vertebra (pro-atlas), but this view has been
disputed by Comet (1888), Chiarugi (1890), and others. Weiss
states that in the white rat the perichordal tissue of this region
gives rise to the tip of the dens epistrophei, but this appears not
to be the case in man. The tissue between the apical ligament of
the dens, and the anterior, alar and crucial ligaments of the atlas
becomes converted into a fibro-adipose tissue. In this there is
ventrally a slight extension of the synovial cavity between the dens
and the atlas and dorsally a greater extension of the cavity between
the dens and the transverse ligament.

The ligaments in the vicinity of the epistropheus are developed
from the periphery of the perichordal tissue and from the inter-
dorsal primitive membranes.

LUMBAR, SACRAL, AND COCCYGEAL VERTEBR2E.

In the earlier stages of development the lumbar, sacral, and
coccygeal vertebrae resemble the thoracic. The blastemal vertebrae
arise each from the contiguous halves of two primitive segments
of the axial mesenchyme. Each vertebra exhibits a body from
which neural and costal processes arise. The neural processes
are connected by ** interdorsal" membranes.

As the blastemal vertebrae become converted into cartilage
specific differentiation becomes more and more manifest. The
cartilaginous vertebral bodies and the intervertebral discs are all
formed in a manner similar to that of the thoracic vertebrae and

MORPHOGENESIS OP THE SKELETAL SYSTEM. 349

except for size manifest comparatively slight differences in form.
The more distal coccygeal vertebrae are, however, irregular. But
the chief specific differentiation is seen in the costal and neural
processes.

The development of the vertebrae of the distal half of the
vertebral column may be followed in Figs. 27^278 (p. 368).

In the lumbar vertehrce radicular, transverse, articular, and
laminar processes arise from the neural cartilages. The radicular
processes resemble the thoracic but are thicker; the transverse
processes are shorter, much thicker at the base, and remain bound
up with the costal processes; the superior articular processes
develop in such way as to enfold the inferior articular processes
of the vertebra next cr anial wards ; the laminar processes are
broad, grow more directly backward than do the thoracic, and on
meeting their fellows in the mid-dorsal line fuse and give rise
to the typical lumbar spines. The mammillary and accessory
processes are developed in connection with the dorsal musculature
and are not definitely formed in cartilage.

In the sacral vertehrce the neural cartilages give rise to very
thick radicular processes; to articular processes, the most cranial
of which develop like the lumbar, while the others long retain
embryonic characteristics ; to transverse processes which in devel-
opment are bound up with the costal processes; and to laminar
processes which are very slow to develop and of which the last
fail to extend far beyond the articular processes.

In the coccygeal vertebrce the neural processes of the first, and
rarely of the second, give rise to cartilaginous plates. From these
only radicular and incomplete articular and transverse processes
arise. The comua of the adult coccyx represent fairly well the
form of the embryonic neural semi-arches.

In the thoracic vertebrae cartilagino'iis ribs develop from sepa-
rate centres in the blastemal costal processes.

In the lumbar vertebrae separate cartilaginous centres prob-
ably also always arise in these processes, but they are developed
later than those of the thoracic vertebrae and quickly become fused
with the cartilage of the transverse processes. The transverse
processes of the adult lumbar vertebrae represent at the base a
fusion of embryonic cartilaginous costal and transverse processes,
but laterally an ossification of membranous costal processes.

In the sacral vertebrae separate cartilaginous costal centres are
developed, but they soon become fused at the base with the trans-
verse processes of the neural cartilages. Laterally by fusion of
their extremities the costal processes give rise to that part of the
sacrum which articulates with the ilium.

In the coccygeal vertebrae the costal processes of the first
vertebra become fused with the transverse processes and develop

350 HUMAN EMBRYOLOGY.

into the transverse processes of the adult coccyx. It has not been
determined whether a separate costal cartilage is developed in
these processes or cartilage extends into them from the neural
processes. The costal processes of the other coccygeal vertebrae
have merely a very transitory blastemal existence.

For a brief period the more distal sacral and the coccygeal
vertebrae have membranous hcemal processes. Schumacher (1906)
describes a haemal arch on the first coccygeal vertebrae which he
considers present in most human embryos 3-5 months old.

Centres of ossification correspond in general with centres of
chondrification, but, as in the case of the vertebral bodies and the
more distal sacral neuro-costal processes, a single centre of ossi-
fication may represent two centres of chondrification.

Period of Ossification.

In the vertebrae, ribs, and sternum one may distinguish pri-
mary and secondary centres of ossification. Most of the primary
centres appear early in intra-uterine life, while the cartilaginous
vertebrae and thorax are assuming a definitive form. The sec-
ondary centres appear after birth.

Vertebrae.

Primary Centres. — There are three primary centres, one for
the body of the vertebra and one for each hemi-arch (Fig. 268, A).
These centres begin to appear at about the same time, but in the
cervical region the centres of ossification in the arches appear
before the centres in the bodies, while in the thoracic and lumbar
regions and, as a rule, in the sacral region, the reverse is true. In
the fetuses studied and tabulated by Mall (1906) the first centres
found were in the second to the eighth neural arches of a fetus
33 mm. long and about 57 days old. In a fetus 34 mm. long and
about 58 days old centres of ossification were found in the arches
of all the cervical and thoracic vertebrae, and in the bodies from
tlie third thoracic to the first sacral. Centres of ossification in the
bodies first appear in the more distal thoracic vertebrae and the
first lumbar.

The centres of ossification in the arches extend from the cer-
vical region distally in fairly regular sequence, although not with
equal rapidity in different fetuses. In one fetus 53 mm. long and
about 72 days old they had extended to the third sacral vertebra
(twenty-seventh spinal vertebra). On the other hand, no centres
were found in the arches of this vertebra in several other fetuses,
73-105 days old. The centres in the arches of the more caudally
situated vertebrae arise generally in the fifth or sixth month.

The centres of ossification in the bodies of the vertebrae extend
cranialwards from the thoracic and caudalwards from the lumbar

MORPHOGENESIS OF THE SKELETAL SYSTEM.

351

region. In a fetus 70 mm. long and about 83 days old they had
extended on the one hand to the epistropheus and on the other to
the last sacral vertebra (Mall). There is considerable variation,
however, in the rapidity with which the centres of ossification
appear in the bodies of the cervical and sacral vertebrae.

The type of ossification in the bodies is endochondral (see
p. 309). The cells at the centre of the body of the vertebra enlarge
and become sharply set off against the intercellular substance.
Finally an invasion of blood-vessels takes place, chiefly from the

Fia. 268.— (After R. Quain, Quam's Anatomy, 10th ed., vol. ii, Pt. 1, Figs. 19, 20, 21. and 22.)
Diagrams to illustrate the development of various vertebnp. A, fetal vertebra; B, thoracic vertebra of
child of two years; C, thoracic vertebra in the seventeenth year; D and E, lumbar vertebra of about
same age; F, atlas before birth; G, atlas in first year; H, epistropheus in fetus of seven months; I, epi-
stropheus shortly after birth; K, sacrum before sixth month; L, saonmi at birth; M. sacrum at about
twenty-third year; N (after Allen Thomson), first sacral vertebra at fourth or fifth year. C, centre of
ossification in the body; C\ coitre of ossification in the dens; Co, centre of ossification in costal element;
Et epiphjrsis; N, centre of ossification in neural arch; V, centre of ossification in ventral arch of atlas.

dorsal periosteum. Calcium salts are deposited in the cartilage
and this is followed by actual ossification in fetuses about three
months of age. In the arches the process of ossification is like-
wise endochondral.^^

The centre of ossification in the body of the vertebra gives
rise to the greater part of the body of the definitive vertebra.
Occasionally the centre may arise as or become divided into two

"In enibr>'()s cleared by the Schultze method the complementary primitive
centres described by Rambaud and Renault do not appear. It is probable that
they were artificially produced by the methods of preparation employed by
Rambaud and Renault (Mall). The primary centres for the neural hemi-arches
are single, not double. See, however, the account of the lumbar vertebrsB (p. 354).

352 HUMAN EMBRYOLOGY.

bilaterally placed centres, one for each half body. This division
may persist in the adult. The centres in the arch give rise to
the posterolateral part of the body of the vertebra and to the
greater part of the arch with its various processes. It is in the
cervical region that the centres in the arch contribute most to the
body. At birth the bones arising from each of the centres of
ossification of a vertebra are separated from one another by car-
tilage. During the first year the centres of ossification in the
neural arches in most of the vertebrae become united dorsally.
This fusion takes place first in the lumbar region. Between the
third and sixth years the bony arches become united to the body.
This fusion takes place first in the thoracic region. The neuro-
central suture lies in a nearly sagittal plane in the' cervical, in an
oblique plane in the thoracic, and in a frontal plane in the lumbar
region.

Secondary Centres; Epiphyses. — Toward the intervertebral
discs the bodies of the vertebrae remain long covered by at layer
of cartilage. About the seventeenth year a centre of ossification
appears in the cartilage on each intervertebral surface. From
each of these centres of ossification a thin epiphyseal disc of bone
arises (Fig. 268, E). The discs fuse with the body about the
twentieth year. The line of suture is visible usually for a year
longer.

The tips of the spinous and transverse processes are covered
during infancy by cartilage. In this cartilage epiphyseal centres
of ossification appear between the sixteenth and the twentieth years
and join the osseous arch after the twentieth year (Figs. 268, C
and D). Similar secondary centres on the dorsal margins of the
superior articular processes and on the costal facettes of the
thoracic vertebrae have been described, but are not generally recog-
nized. (See Poirier and Charpy, Traite d'Anatomie, vol. i, p.
342, 1899.)

Cervical Vertebrce. — ^In most of the cervical vertebrae, accord-
ing to Leboucq (1896), the ventral limb of the transverse process
is ossified by ingrowth at one end from the radix, on the other from
the tip of the transverse process. In the seventh cervical vertebra
frequently, in the sixth occasionally, and in the fifth and fourth
rarely, there may arise during the second to the fifth month a
separate centre of ossification for the costal element. While this
costal element may remain free as a cervical rib, it usually becomes
fused with the osseous projections from the radix and the trans-
verse process (Figs. 269, A and B). Except in the seventh cer-
vical vertebra the epiphyses of the spines are usually double.

Atlas, — The posterior arch and the lateral masses of the atlas
are ossified from two bilaterally placed centres which correspond
to the centres of the neural arches of the other vertebrae (Fig.

MORPHOGENESIS OP THE SKELETAL SYSTEM.

353

268, F). In the anterior arch one, or sometimes apparently two,
centres of ossification appear during the first year after birth (Fig.
268, G). The dorsal union of the osseous neural arch pieces occurs
between the third and fifth years. Often a separate centre of ossi-
fication appears in the spinous process before the neural arch
pieces are united (Quain). The union of the posterior with the
anterior arch occurs between the fifth and ninth years.

Epistropheus. — The neural arch and the body are ossified
essentially as in the other cervical vertebras except that occasion-
ally there are two bilaterally placed centres in the body. The
odontoid process becomes ossified from two bilaterally placed
centres which appear in the fourth or fifth fetal month and soon

A

Fio. 269. — (After T. Dwight, Piereors Human Anatomy, 1907, Fig. 168.) Diagrams illustrating
the homology of the costal elements. A, sixth cervical vertebra; B, seventh cervical vertebra; C, fifth
thoracic vertebra; D, second lumbar vertebra; E, fifth lumbar vertebra; F, transverse section through
sacrum. The costal elements are stippled.

fuse together (Fig. 268, H and I). These centres furnish material
for a part of the superior articular processes. Between the fourth
and sixth years the odontoid process becomes joined to the body
and the radices of the arch, first laterally and then ventrally and
dorsally. Between the centre of the base of the odontoid process
and the body of the epistropheus a disc of cartilage remains till
late in life. The apex of the odontoid process is formed from a
separate centre of ossification, which appears in the second year
and is joined to the main part of the process about the twelfth
year. This apical piece probably represents an epiphysis. There
are also said to be rudiments of a cranial epiphysis of the body of
the epistropheus, but this statement is not generally accepted. A
caudal epiphysis of the body is constant.

Lumbar Vertebrce. — The mammillary processes of the lumbar
vertebra^, of the first sacral vertebra (Fawcett, 1907), and of the
twelfth thoracic vertebra have special epiphyses, which appear
about the time of puberty or a little later and join the rest of the

Vol. I.— 23

354 HUMAN EMBRYOLOGY.

vertebrae after the eighteenth year (Fig. 268, D). Somewhat rarely
the costal element of the first lumbar vertebra has a separate
centre of ossification, which appears early in fetal life. It may
remain free as a lumbar rib. Sometimes in the fifth lumbar ver-
tebra, and very rarely in some of the others, there are found two
centres for the arch on each side; one for the radix, transverse
process, and superior articular process, the other for the lamina,
inferior articular process, and spine. According to Poirier and
Charpy (Traite d'Anatomie, 1899), the fifth lumbar vertebra has a
special epiphysis for the anterior tubercle of the transverse
process.

Sacrum. — The usual primary centres are found for each of
the five sacral vertebrae, one for the body and one for each neural
hemi-arch. In addition there are separate centres for the costal
elements of the first three or four vertebrae (Fig. 268, K and L).
Sometimes, apparently, costal centres are found merely in the first
two sacral vertebrae, sometimes in all five. Changes preliminary to
ossification occur both in the bodies and in the neural processes
of the sacral vertebrae at a period quickly following their appear-
ance in the lumbar region. Actual ossification in these centres in
the more distal vertebrae, as a rule, does not take place until a
considerably later period, usually not until the fourth month in
the bodies and the fifth or sixth in the arches. The centres in the
arches join those of the bodies between the second and sixth years.
The more caudally -situated join before the more cranially situated.
Union of the laminae with one another takes place from the seventh
to the fifteenth years. It takes place first in the more cranially
situated vertebrae, frequently does not occur in the fourth and
seldom in the fifth. The centres for the costal elements of the first
three vertebrae arise usually, according to Posth, in the fifth, sixth,
and seventh fetal months respectively. That for the fourth ver-
tebra does not usually arise until tiie third month after birth.
There are considerable variations in the time of origin. The costal
centres unite with those of the neural arches between the second
and fifth years. They unite with the bodies slightly later than
with the arches. Rambaud and Renault (1864) describe special
centres which are said to arise in the sixth month in the transverse
processes. Posth could not confirm this.

In addition to these primary centres there are epiphyseal
plates for each body and two for each lateral sacral margin, one
for the auricular surface and one for the rough edge distal to this
(Fig. 268, M). According to Poirier (Traite, 1899), the auricular
epiphyseal plates arise from the fusion of the epiphyses of the
transverse processes. Fawcett (1907) describes them as arising
from four costal epiphyses belonging to the first two sacral verte-
brae. The tuberosities he describes as arising from the costal

MORPHOGENESIS OP THE SKELETAL SYSTEM. 355

epiphyses of the third and fourth sacral vertebrae and transverse
epiphyses of the fourth and fifth. The epiphyses of the bodies
begin to arise about the fifteenth year and those of the auricular
plate between the eighteenth and the twentieth years. Epiphyses
for each of the tubercles of the spinous processes are described
by Rambaud and Renault, 1864, and Fawcett, 1907. Fawcett
describes twelve costal epiphyses, eight epiphyses belonging to
the transverse processes, two to the mammillary processes and
three to the spinous processes.

The sacrum begins to be consolidated about the time of
puberty. The costal processes on each side fuse with one another.
This is followed by union of the epiphyses with the bodies and by
ossification in the intervertebral discs. The process begins cau-
dally and extends in a cranial direction. The bodies of the first
and second sacral vertebrae usually become united about the twenty-
fifth year but the centres of some of the intervertebral discs may
persist longer than this. The lateral epiphyseal plates unite about
the twenty-fifth year.

For the recent literature on the development of the sacrum see Posth (1897)
and Fawcett (1907).

Coccygeal Vertebrce. — Ossification in the coccygeal vertebrae
usually takes place after birth. Each is ossified from a single
centre. The centre for the first vertebra usually appears in the
first year but may appear much later, that of the second appears
from the fifth to the tenth year, that for the third just before and
that for the fourth just after puberty. The three more distal ver-
tebrae usually become united with one another before being joined
to the first. This latter union may not occur until the thirtieth
year. The first coccygeal vertebrae not infrequently becomes united
to the sacrum. In old individuals the whole coccyx is often united
by bone to the sacrum, more often in men than in women.

According to some authors, there are two epiphyseal plates
for each of the bodies of the first four coccygeal vertebrae and in
addition separate centres of ossification for each of the comua
of the first vertebrae.^* Two centres of ossification for the fifth
coccygeal vertebra, one for the body and one for an epiphysis, are
also described as arising in the tenth year (Poirier and Charpy,
1899).

Ribs.

Ossification begins in the ribs before it does in the vertebrae.
Centres appear in the bodies of the sixth and seventh ribs toward
the end of the second month and then rapidly come to view in the

"According to Poirier, the primary centres appear in the fourth or fifth
year in the first vertebra, in the sixth to the ninth year in the second, third and
fourth. The epiphyseal plates appear from the sixth to the twelfth year.

356 HUMAN EMBRYOLOGY.

other ribs. The centre in the first rib usually appears before that
in the twelfth. All are usually present by the end of the second
month, but that in the twelfth may not appear until later. In
two specimens out of 29 fetuses with an estimated age of 55 to
110 days, Mall (1906) found a centre of ossification in the costal
element of the seventh cervical vertebra.

The osseous nucleus arises near the angle of each rib and
extends rapidly toward the head. At the end of the fourth month
the osseous shaft of the rib bears about the same proportional
relation to the costal cartilage which it has in the adult. About
puberty epiphyseal centres arise, one for the articular surface of
the head, one for the articular surface of the tubercle, and one for
the non-articular surface of the tubercle. FVequently only one epi-
physis seems to arise on the tubercle (Fig. 270). Usually no tuber-

FiG. 270. — (After R. Quain, Qiutin's Anatomy, 10th ed., vol. ii, Pt. I, Fig. 31.) Diagram to illus-
trate the epiphyHes of the head and tubercle of one of the mid-thoracic ribs at about the twentieth year.
1 , body ; 2, epiphysis of the head ; 3, that of the tubercle.

cular epiphysis is found on the eleventh and twelfth ribs. The
union of the epiphyses with the shaft takes place after the twen-
tieth year. The epiphysis of the head does not usually join before
the twenty-fourth year.

The centres of ossification of the ribs are subperiosteal in
character.

In the adult the first costal cartilage may become partially or
completely covered by a superficial layer of bone. Late in life
the other costal cartilages may become thus covered, especially on
the superficial surface. This process is more frequent in men than
in women (Quain).

Sternum.

Ossification in the sternum begins considerably later than
in the ribs. The centres of ossification are variable in the
time and place of their appearance (Fig. 271, B and D). About
the middle of the sixth fetal month a centre usually appears in
the manubrium. Often other accessor}^ centres appear (Fig.
271, D). Thus Mayet (1895) in fourteen stemums out of eighteen
found one or more accessory centres in the manubrium; in ten
instances one extra centre situated caudalwards from the main

MORPHOGENESIS OF THE SKELETAL SYSTEM.

357

centre ; in four instances two or more accessory centres. In addi-
tion there are two epiphyseal centres next the sternoclavicular
joints. These fuse with the manubrium between the twenty-fifth
and twenty-eighth years. The body of the sternum is usually
ossified from five or from seven centres. The segment next the
manubrium is usually ossified from a single centre which appears
in the seventh month. The next segment may be ossified from a
single centre or from a pair of centres. The last two segments
most frequently are each ossified from a pair of centres, but may
be ossified from a single centre. As a rule, all the centres of ossi-
fication except those in the last segment are present at birth and
these last appear during the first year after birth. By the sixth
year the centres of each pair usually have become fused with one
another. Glenerally the various osseous segments of the body of

lo. 271.— (Att«- R. Quain. Qudii.

'. ABBtomy,

imhed.

.vol.

CMaficatioD o! th« Btemum. A.

ium ■nd Gnt three etemsl iKcme.

of osulic eeolreBl E, example ol

BUraum;

•ep

i. Ft. 1. Fi|. 30.) Diasnun illustnt-

the sternum become united in the 12-25 years, but lines indicating
the boundaries between them remain till late in life. The manu-
brium and body rarely fuse; according to Gray, in about 6 or 7
per cent, of cases after 60 years of age. There may be a foramen
in the sternum due to lack of fusion of a pair of centres of ossifica-
tion or to failure of a centre of ossification to develop (Pig.
271, E).

Four times out of twelve Mayet foimd the bilaterally placed
centres of the body fused vertically with those of their own side
before the fusion of pairs across the median line had taken place."

The ensiform process is ossified from a single centre which
appears late, usually not before the sixth year, and rarely trans-
forms the whole process into bone. The centre of ossification
arises at the base of the process. The osseous ensiform process is
usually united to the body in middle life.

" See Markowski, 1902, 1905, for a somewhat different description of the
ossification of the slernum.

358 HUMAN EMBRYOLOGY.

Relative Length of the Different Regions of the Spine

during Development*

In 1879 Aeby contributed an important paper dealing with the length
of the various regions of the spinal column at different ages, with the height
of the constituent vertebrae and with the thickness of the intervertebral discs in
man. He showed that in young embryos the cervical region is relatively much
longer, the limabar much shorter than in the adult. These results have been
confirmed by Moser (1889), Ballantyne (1892), and others. It has been shown
by Bardeen (1905) that, in embryos during the second and third months of
development, if the length of the thoracic region be taken as 100 the length
of the cervical region is about 60, the lumbar from 40 to 50, the sacral from
33 to 42.5. In the adult the cervical region has been estimated at from 41.7 to
47.5, the lumbar from about 56.3 to 71.6, the sacrococcygeal from 61 to 68.
(See Ravenel, 1877, Aeby, 1879, Tenchini, 1894, Dwight, 1894 and 1901.)

Curvature of the Spinal Column during Development.

During the first month of embryonic development the spine acquires a
marked ventral flexion (see 2, Fig. 272). From this period until the time of
birth the cervico-thoraco-lumbar region of the spine, at first rapidly and then
more gradually, becomes straighter (109, 144, 108, 145, 184, Fig. 272). The sacral
region also becomes much straightened during the second and third month
of embryonic development (109, 144, 108, 145, 184, Fig. 272), but subsequently
acquires a second ventral flexion (Ad, Fig. 272). During the latter half of
embryonic development there takes place a marked dorsal flexion at the lumbo-
sacral border (184, Fig. 272). After birth and the assimiption of the erect
position dorsal flexion takes place in the cervical and the lumbar regions (I and
Ad, Fig. 272).

Number of Vertebrae and Regional Differentiation*

At the period of greatest development of the caudal extremity of the human
embiyo thirty-six vertebne usually are present. This stage is reached in embryos
from 8-16 mm. in length. Occasionally the number of vertebrsB may reach thirty-
seven. Beyond the last vertebra the chorda dorsalis extends for some distance
distally (Fig. 273).

Regional differentiation, as already pointed out, becomes well marked toward
the latter part of the blastemal period. The thoracic region is clearly demarcated
by the great development of the costal processes of the thoracic vertebrsB. The
sacral region becomes definitely marked when the blastema of the sacrum comes
into contact with that of the ilium. According to Rosenberg (1877, 1899, 1906),
the costal processes of the seventh cervical and the first lumbar vertebra at the
period of chondrification are to be regarded as ribs, so that in subsequent
development there is a reduction in the number of thoracic vertebrae. While
each costal element of the seventh cervical vertebra has a centre of chondrification
like a true rib, and near the body of the vertebra appears enough like a rib
to be called a " rudimentary rib," one is not more likely to mistake it for the
first rib than one would be to mistake the costal element of the seventh cervical
vertebra in the adult for a true rib. This is even more true of the costal element
of the first lumbar vertebra. Although this normally probably has a separate
centre of chondrification, it has distinct characteristics which sharply demarcate
it from the twelfth thoracic rib, characteristics of form as well as of size. (See
Figs. 261 and 262, from an article which has been cited by Rosenberg in support
of his hypothesis.)

MORPHOGENESIS OP THE SKELETAL SYSTEM.

359

According to Rosenberg, the saemm is composed at first of a more distal
set o£ vertebrs than those belonging to it in the normal adult condition; in
other words, the iliac attachment of the skdeton of the limb is supposed to
advance cranialwards along the spinal column during ontogeny. The studies of
Holl (1882), Paterson (1893), Bardeen (1904), and others have shown that the
views of Rosenberg do not correspond with the conditions found in the majority
of the human embryos and fetuses, at the period under discussion, which have
been carefully studied.

Fio. 272.— DiAgram to show the ourvftture of the spinal oolumn, the proportional lengths of the
various regions, the relations of the acetabula to the sacral region, and the direction of the long axis of the
femur in a series of embryos and fetuses 7 to 50 mm. in length, in an infant and in an adult. Each curved
line represents the choida dorsalis of an individual. The cervical, lumbar, and coccygeal regions are repre-
sented by the heavy, the thoracic and sacral by the light portions of the line. The approximate position
where a line joining the coitres of the two acetabula would cut the median plane is represented at a. For
Embryo II, in which the skeleton of the inferior extrmnity is not yet differoitiated, the position of the
future acetabula is deduced from Embryo CLXIII, length 9 mm. The line passing in each instance from
a and terminating in an arrow point represents the long axis of the femur. For Embryo II this line is
pointed toward the centre of the tip of the limb-bud. From a in each instance a perpendicular is dropped
to a line connecting the two extrmnities of the sacral region. The numbers refer to the following embrsros
and fetuses in the collection of Professor Mall: 2. II, length 7 mm.; 109, CIX. length 11 mm.; 144,
GXLIV, length. 14 mm.; 108, CVIII, length 20 mm.; 145, CXLV, length 33 mm.; 1S4, CLXXXIV,
length 50 mm.; I new-bom infant; Ad, Adult.

Variation in the number of vertebraB belonging to each of the regions of
the spinal column occurs in the embryo as well as in the adult. Bardeen (1904)
reaches the conclusion that the frequency of variation in the embryo is probably
the same as that in the adult. Before this is definitely decided a much greater
number of embryos must be studied than are at present on record. Regional
variation in the embryo and fetus must not be confounded with the normal
changes taking place in the development of the costal elements of the vertebrae
of the cervical and lumbar regions. A separate centre of chondrification in the
costal element of the first lumbar vertebra does not indicate a lumbar rib unless
the costal process and the centre of chondrification resemble morphologically the
twelfth thoracic rib so that there is no sudden change of form from the one
to the oth^r.

360 HUMAN EMBRYOLOGY.

Comparative Development of the Vertebrte.

For an account of the embryological development of the vertebne in the
tower vertebrates and a summary of the literature relating to the subject the
exeellent article by Schauinstand in Hertwig's Handbuch der Entwickelungsge-
sehichte der Wirbeltiere should be cousulted. In the anamniotes, the chorda
dorsalis plays a relatively much greater part than in the amniotee, and in the
sauropsida a mueh greater part than in the mammals. Primitively there are
apparently four areh pieces developed on each side in each sclerotome, two dorsal
and two ventral. As a rule, the cranially situated dorsal and venlral arch pieces

Fia. 273.

-(Aft

«rHsi

nuon, leOI.) S^ttAl

euttlm

.ugh th.

: caudal end

uf ao embrj-c

(No.

144 of the

i/enliM

Magn. Bl : 1.

The chorda

bify.

;ube™:t™dinlo

(iiment ot the tail.

ThetoUlr

iucb^rc

jf vert«brw In

thirty-ai.. wv

Th«e dd E

,ot Htaid into the

dnJ upp

Hidage,

ncnlis media);

CA..

xtonulle; Fil.caud.

mcaudi

lie; A/«i...[«iuJcord;

S. ufl., wnus 1

V.c.<

i.. yens ca

v« in(

trior t

V. ucniix media).

of each sclerotome are incomplete while the caudally situated arches are firmly
united to the sheath of the notochord. In the amniotes the cranial arch pieces
of one sclerotome unite with the caudal of the sclerotome next cranialwards to
form the definitive vertebral arches and arch bases. The bodies of the vertebra
develop between the regions of attachment of the arches to the chorda. The
neural and articular processes come from the dorsal arches, the transverse, costal,
hiemal, and hypochordal (see p. 345) processes from the ventral arches.

In the development of the human vertebne the caudal dorsal and ventral
arch aniages of each sclerotonie arise simultaneously and are soon united by a
common base or cbordal proc«s6 to the mesenchymal sheath about the notochord.
The cranial dorsal and ventral arch aniages arise later, the dorsal becoming the

MORPHOGENESIS OF THE SKELETAL SYSTEM. 361

interdorsal membranes, the ventral the interventral membranes. The cartilages of
the bodies develop about the notochord between the bases of the cranial and caudal
ventral arch anlages. But one centre of chondrification appears to give rise to
the definitive vertebral hemi-arch, although a separate centre arises for the costal
process.

The ossification of the definitive vertebrae varies so in different classes
of vertebrates that no comparison of the process will be attempted here.

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MORPHOGENESIS OP THE SKELETAL SYSTEM. 363

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366 HUMAN EMBRYOLOGY.

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D. SKELETON OF THE LIMBS.

One of the most studied subjects in morphology has been the
development of the vertebrate limbs. Since, fortunately, critical
summaries of its literature have recently been given by several
noted investigators, among whom may be mentioned Wiedersheim
(1892), Mollier (1893, 1895, 1897), Gegenbaur (1898), Rabl (1901),
Fiirbringer (1902), Ruge(1902), and Braus (1904), no attempt will
be made here to review this work except so far as it deals directly
with the development of the human limb.

During the third week of embryonic life the limb buds become
filled with a vascular mesenchyme. The source of this tissue is
uncertain. In part it may come from the primitive body-segments,
but it seems probable that in the main it comes from the parietal
layer of the unsegmented mesoblast. Toward the end of the fourth
week a slight condensation of the mesenchyme can be seen at the
centre of the arm bud, and early in the fifth week a similar conden-
sation may be noted in the leg bud. This condensation represents

MORPHOGENESIS OF THE SKELETAL SYSTEM. 367

the first rudiment of the skeleton of the limb. The tissue com-
posing it may therefore be called * * scleroblastema. " From the
scleroblastema there is developed a membranous skeleton. In this
a cartilaginous skeleton is differentiated, and this in turn is re-
placed by the permanent osseous skeleton. We may thus distin-
guish three overlapping periods, a blastemal, a chondrogenous, and
an osseogenous. We shall first consider in some detail the devel-
opment of the skeleton of the inferior extremity and then more
briefly that of the superior extremity.

INFERIOR EXTREMITY.

Blastemal Period.

At the time when the condensation takes place in the leg bud
the latter has the general form shown in outline in Fig. 274. The
bud projects considerably from the body, but shows no definite
resemblance to the limb to which it is to give rise. The condensed
tissue, scleroblastema, is not sharply outlined. It represents the
region of the acetabulum and the proximal end of the femur.

Once begun, skeleton differentiation proceeds rapidly. In
an embryo 11 mm. long (Fig. 275) it may be seen that from the
original centre of skeletal formation the condensation of tissue has
extended both distally and proximally, but much more freely in the
distal direction. Distally the scleroblastema shows femur, tibia,
fibula, and a foot-plate; proximally, an iliac, a pubic, and an ischial
process. A series of sections through the skeletal mass shows
that in the femur, tibia, and fibula chondrification has begun. At
centres in the blastema of the ilium, ischium, and pubis a still
earlier stage of chondrification has made its appearance. The leg
of this embryo, therefore, represents a stage of transition from
the blastemal to the chondrogenous stage of development.

Chondbogenous Period.

The further development of the skeleton of the limb during
the second and third months of intra-uterine life may be followed
in Figs. 276, 277, and 278. For the sake of convenience the devel-
opment of the several parts of the skeleton will be taken up as
follows: (a) the os coxae; (6) femur, hip-joint, tibia and fibula,
and knee-joint; (c) ankle and foot.

(a) The Os Coxm. — The pelvic scleroblastema of embryos of
the stage illustrated in Fig. 275 undergoes a rapid development.
Its iliac portion extends in a dorsal direction toward the vertebrae
which are to give it support. The costal processes of the latter at
the same time become fused into a dense mass of tissue which
enters into close association with the iliac blastema (Fig. 276),

HUMAN EMBRYOLOGY.

FlOB. 274-278.— (After Bardeen, Amer. Journ, of Anat.. 1905.) Lateral view of modda to illugtn
the development of the dialnl pBrt of the spinal column and of the inferior extremity of embryos B-
mm. loDK, In Firs. 27*. 275, and 276 the sderoblaatems i! «honn, and in this in KiEs. 275 and 276 I
centres of chondrification. In FigP. 277 and 278 the Partilaginous afceleton ia shown, and in this in F
27Brentr«9 0fo99iliCBtion.

Fig. 274, Length of embryo, 0 mm. Fig. 275. I-ength of embryo. 11 mm. Fin. 270. Length of e
bryo. 14 mm. Fig. 277. Length of emhryo. 20 mm. Fig. 278. Length of fetus. SO mm. Chd,. ehoi
dorsalis; Co", first eoeeygeai vertebia; Cnifa /*, iwcHih rib: Fi, fibular F.o., foramen obturatum; .
ilium; L.i., ligBmentum inguinale: M.id., membnns interdorsalin: P.. pubis; Pr.a.o.. proee.wus artii

pmcessus tmnaverBUs ; Ti, tibia.

MORPHOGENESIS OF THE SKELETAL SYSTEM. 369

although for some time separated from this by a narrow band of
tissue staining less densely than the blastema. Cranialwards the
iliac blastema extends toward the abdominal musculature, to which
it finally gives attachment.

While the blastemal ilium is thus becoming diflferentiated the
pubic and ischial processes of the pelvic blastema extend rapidly
forward. Ventral to the obturator nerve they become united by
condensed tissue, which completes the boundary of the obturator
foramen. Betwen the crest of the ilium and the ventral extremity
of the pubis dense tissue is formed to give attachment to the oblique
abdominal musculature. This represents the embryonic inguinal
ligament and completes a femoral canal (Fig. 276).

While the blastemal pelvis is being completed the three centres
of chondrification, barely visible in the 11 mm. embryo, give rise
respectively to iliac, pubic, and ischial cartilages in which the adult
form becomes gradually more distinct. (Compare Figs. 276, 277,
and 278.) In embryos between 15 and 20 mm. long each of the
three cartilages gives rise to a plate-like process over the head of
the femur. These processes fuse with one another and give rise
to a shallow acetabulum (Fig. 277), which during the third month
gradually becomes deeper (Fig. 278). The iliac and ischial car-
tilages furnish a greater part of the floor of the acetabulum
than the pubic cartilage and unite with one another before being
joined by the pubic cartilage.

Toward the end of the second month and the beginning of the
third month of development the symphysis pubis is formed. This
is at first composed of dense blastemal tissue. In this tissue first
hyaline and then fibrocartilage become diflferentiated. At the
centre of the joint a slight fissure may appear in adult life (Fara-
beuf, 1895).

(6) Femur and Hip- joint. Tibia, Fibula, and Knee-joint. —
The rapid development of the blastemal skeleton of the lower limb
has been briefly described above. Soon after the anlage of the
femur makes its appearance condensation of tissue marks out the
anlages of the tibia and fibula and the skeleton of the foot. This
last seems to be at first a somewhat irregular continuous sheet of
tissue. It is not clear whether or not the anlages of the tibia and
fibula also begin as a continuous sheet which becomes divided, by
ingrowth of blood-vessels, into tibial and fibular portions. The
incomplete development of the interosseous fissure in an 11 mm.
embryo suggests this (Fig. 275). The blastemal anlages of the
tibia and fibula are here very incompletely separated.

Within the blastema of the femur, tibia, and fibula chondrifica-
tion begins as soon as the outlines of the blastemal skeleton are
fairly complete (Fig. 275). The embryonic cartilage appears
slightly knee- wards from the centre of the shaft of each bone and

Vol. I.— 24

370 HUMAN EMBRYOLOGY.

then eKtends toward the ends. The cartilage of the femur consists
of a bar largest at the knee, whence it tapers off toward the hip.
The cartilages of the lower leg lie nearly in a common plane. That
of the tibia is larger than that of the fibula and toward the knee
it broadens out considerably. At this stage the joints consist of
a solid mass of mesenchyme (Figs. 279 and 280). The tissue

Fig.

.384.

Fi<».

276-28*.-

(Aft

er BBrdesD. Amer. J

Fourn

. of Anlt.

. i90a.)

Fi,. 279. ,

Becfjon

3ugh the

livuid loo

■tot J

«,«nbry(

l™.

Th< MMJon di>« not

thiongh til

inllmB

the fin<t

Fit

ction through 1

iibiK, iBchium, femur.

fibula, ol<i

,.. cube

lid, «nd foiirt

h meUtarsBl of an embryc

lona.

Fig.

281. Seciion thi

vu^b

tbt knee-jo

.bry

lone. Fi«.

282.

Section tl

1 rough ti

lelinee-joiBt

odn embryo 33

long. Fi(.

. Secli<

DH tl

hirough tl

le kne^joiQ

■i,. unci to

of an e

mbry

o 14 mm. Ion,.

FiS;

2M. Bectio

.Dth.

heh

tim embryo

30™

C«.. eub«d : F.

ir ; Fi., fibuin ; F.Pl.,

foot-plsM ;

II..

ilium:

/..,

i«hiuro;

; P.. pubis;

Lj..

, li,. .««

: 4, met!

>Ur»l(

iquai

turn.

uniting the femur and tibia has temporarily somewhat the appear-
ance of precartilage (Fig. 283). From this period onwards the
development of the individual bones and joints is rapid.

The cartilaginous femur expands at the expense of the sur-
rounding blastemal perichondrium and at the same time acquires
adult characteristics (Figs. 276, 277, and 278).

Tlie hip-joint is at first completely filled with a dense blastemal
tissue (Fig. 280). While the embryo is growing from 20 to 30 mm.
in length, cavity formation begins in the tissue lying between the

MORPHOGENESIS OF THE SKELETAL SYSTEM. 371

cartilaginous floor of the acetabulum and the head of the femur.
The first stage in the process is marked by a condensation of the
capsular tissue immediately bordering upon the joint and of the
perichondral tissue which at this stage covers the cartilages on
tiieir articular surfaces as well as elsewhere. In the region of
the ligamentum teres a fibrous band is likewise differentiated from
the blastema of the joint. The rest of the tissue becomes looser
in texture and ultimately is absorbed (Fig. 284). Henke and

Fio. 2S7. Fio. 288.

Flos. 285 Ui 2B8.~(AfCa- Schulin, Arohiv {. Asatoici*. 1879.)

Fig. 285. Mcdiui SMtlon tlirouih th« knw-joiDt of a letut 13 on. lon(. a. p«MUb; b. a

286-288. Hip-joiat of s msle fetus '25 cm.'lonK, of it fenale cjiild six yean old, and of a male ndult. a.

(wnfication ; d, epiphyseal aaxeoiis nudeiu : (, ligamentum teres.

Eeyher (1874) gave a good account of the development of the
hijKJoint. Moser (1893) has described that of the ligamentum
teres. Schulin (1879) has given a good account of the later devel-
opment of the joint cavity in its relations to the head and neck of
the femur (see Figs. 286-288). It is to be noted that in the fetus
25 cm. long (Fig. 286) the joint cavity extends about the neck of
the femur in a pocket lined on one side by perichondrium, on the
other by the capsule of the joint, and that later the peridiondral
lining becomes periosteum (Fig. 288).

372 HUMAN EMBRYOLOGY.

The tibia and fibula at first lie nearly in the same plane (Fig.
275). As the head of the tibia enlarges toward the knee-joint it
comes to lie ventral to the proximal extremity of the fibnla. This
may be seen in Figs. 276 and 277.

The development of the knee-joint in man has been studied by
a number of competent observers. Bernays (1878) gave a good
review of the previous work of von Baer, Bruch, Henke, and
Reyher, and an accurate description of the processes which take
place. Of the more recent articles those of Schulin (1879), Kaz-
zander (1894), and Lucien (1904) deserve mention.

Until the embryo reaches a length of about 17 mm. the knee-
joint is marked by a dense mass of tissue (Fig. 279). The medul-
lary tissue at the knee, like that at the hip and other joints, is less
dense than the surrounding cortical substance, so that when the
cartilages of the femur, tibia, and fibula are first differentiated they
seem to be connected by a tissue which, in some respects, resembles
the cartilage of which they are composed (Fig. 283) ; but as the
cartilages become more definite the apparent continuity disap-
pears. As the musculature becomes differentiated a dense tendon
for the quadriceps is formed in front of the knee-joint. At this
period the joint is flexed at nearly a right angle.

In embryos of about 20 mm. the tissue immediately surround-
ing the cartilages becomes greatly condensed into a definite peri-
chondrium. The peripheral blastemal tissue at the joint becomes
transformed into a capsular ligament, strengthened in front by
the tendon of the quadriceps. Within the joint most of the tissue
begins to show signs of becoming less dense, but the menisci and
the crucial ligaments, like the ligaments of the capsule, are differ-
entiated directly from the blastema (Figs. 281 and 282). In the
differentiation of the articular blastema the menisci first become
distinct, then the capsule, then the crucial ligaments, the patella,
and the lig. mucosum.

A knee-joint cavity first appears, in embryos about 30 mm.
long, between the patella and the femur. According to Lucien,
two other cavities somewhat later appear between the condyles
of the femur and the menisci. These cavities secondarily communi-
cate with the retropatellar cavity and with cavities formed between
the menisci and the tibia. The cavity of the knee-joint is primi-
tively partly divided into two parts by a median septum (lig.
mucosum), which becomes greatly reduced in fetuses 10-12 cm.
long (Fig. 285, C) and in the adult is replaced by a fat pad.

The shafts of the tibia and fibula are incompletely separated
in the blastemal stage. The cartilages which arise in the sclero-
blastema are, on the other hand, separated by a distinct interval
(Fig. 279). At first short and thick, the shafts become gradually
more slender in proportion to their length. The fibula, at all times

MORPHOGENESIS OF THE SKELETAL SYSTEM. 373

smaller, becomes increasingly more slender in comparison with
the tibia. In fetases 50 mm. long (Fig. 278) both bones, and espe-
cially the fibula, are still relatively thick compared with the adult
bones.

During a period of rapid development, in embryos of 15 to
20 mm., the tibia and fibala, like the femur, may extend so rapidly
in length as to become temporarily distorted by resistance at the

Fia. 388.— (After R. Quoin. Qutin'a Anatomy, lOth «d„ vol. ii. Ft. I. Fign. 1S7 ud 158.) Osafi-

A. Bone st birth. B. Child under ax yean of ave. C. Child two to thres yean older thu B. D.
PenoD of about twroty years. E. Acetabular resion of hip-bone at tourtaen yean of afe. 1. ililiro; 2,
ixchium: 3, pubis; 4. oa aoeUbuli; S. bony nodules between ilium and ischiuni: 6 and 7, epiphyBeal
lamins on ilium and ischiuni; S, 9, 10. 11, epiphyseg of aolerior inferior iliac spine, iliac crest isohial
tuberosity, and gympbysia putni.

ends. This is often especially marked in hardened specimens.
Holl (1891), Sohomburg (1900), and others have called attention
to this distortion.

(c) Ankle and Foot. — Of the papers dealing with the early
development of the skeleton of the human foot the more important
are those of Henke and Reyher (1874), Leboucq (1882), v. Bar-
deleben (188.3, 1885), Lazarus (1896), and Schomburg (1900).

During the fifth week of embryonic development the free ex-
tremity of the limb bud becomes flattened and differentiated into
a foot-plate (Fig. 275). Toward the end of the fifth week the
anlages of tlie individual bones of the ankle and foot begin to

374

HUMAN EMBRYOLOGY.

become marked by specific condensation of the blastemal tissue.
Within these anlages precartilage soon appears. The digital rays
are marked at first by condensed bars of tissue, in which segmenta-

yw.Mt-

E

Fio. 290.— (After R. Quain, Quain's Anatomy, 10th ed., vol. u, Pt. I, Fig. 169.) OssificaUon of
the femur. A. Before the eighth month. B. At birth. C. About a year old. D. At about the fifth
year. £. Near the age of puberty. 1, diaphysis; 2, distal epiphysis; 3, head; 4, great trochanter;
5, small trochanter.

tion into metatarsals and phalanges appears during the period
of chondrification (Fig. 276). The metatarsal cartilages become
differentiated before the tarsal cartilages. The phalangeal car-
tilages appear relatively late.

Fig. 291.— (After R. Quain, Quain's Anatomy, 10th ed., vol. ii, Pt. I. Fig. 160.) Ossification of
the tibia. A. Some weeks before birth. B. At birth. C. At the third year. D. Betweoi the eighteenth
and twentieth years. E. Example of separate centre for tuberosity. 1, diaphysis ; 2, proximal epiphy>
sis ; 2*, epiphysis of tuberosity; 3, distal epiphysis.

The earliest appearance of the tarsal cartilages is found in
an embryo about 14 mm. long (Fig. 276). Toward the end of the
second month these cartilages become much more distinct (Fig.
277). By the middle of the third month the cartilages of the foot
have a form distinctly corresponding to the adult. The similarity
is still better marked at the end of the third month (Fig. 278).

MORPHOGENESIS OF THE SKELETAL SYSTEM.

375

The joint cavities begin to develop while the embryo is grow-
ing from 25 to 30 nun. in length. As in other cases, so here the
blastemal tissue in which the cartilages are developed becomes
condensed at their articulating ends and about the joint, while in
the region of the joint the tissue becomes less dense and finally
disappears, leaving a joint cavity. In embryos of about 30 mm.
the joint cavities of the foot are filled with a loose fibrous tissue ;
in fetuses of 50 nun. definite
cavities are to be made out.

During the progress of
form differentiation above
described, the shape of the
foot is markedly altered. At
the beginning of the devel-
opment of the foot the tar-
sal and metatarsal bones lie
nearly, though not quite, in
the same plane as the bones
of the leg. They are so ar-
ranged, however, that the foot
is convex on its dorsal surface
and concave on the plantar,
and the projections of the
calcaneus and talus serve to
deepen the plantar fossa. The
metacarpals spread widely apart. As differentiation proceeds, the
metatarsals come to lie more nearly parallel to one another, and
the tarsal elements become compacted in such a way as to give
rise to the tarsal arch. The foot at the same time is dorsally flexed
at the ankle and slightly everted. The toes are flexed. In the
further development of the skeleton of the foot the various con-
stituent structures are elaborated, and the foot gradually becomes
more flexed dorsally and turned toward the fibular side.

Fio. 292.— (After R. Quain, Quain's Anatomy, 10th
ed., vol. ii, Pt. I, Fig. 161.) Oaflification of the fibula.
A. At birth. B. At about two yean. C. At about four
years. D. At about twenty years. 1, diaphysis; 2,
distal epiphysis; 3 proximal epiphysis.

Period op Ossification.

The hip-bone is ossified from three primary centres, one for
each of its constituent parts, the ilium, ischium, and pubis, and
from several epiphyses. There is one primary centre of ossifica-
tion for each of the other bones of the inferior extremity, and in
addition most of the bones have one or more epiphyses. In the
tarsus the calcaneus alone regularly has an epiphysis. The patella
has no epiphysis. With the exception of those of the tarsal
bones and of the various sesamoid bones the primary centres
of ossification appear relatively early in intra-uterine life. At
birth there are usually centres of ossification present in the cal-
caneus, talus, and cuboid, but not in the other tarsal bones. Ossi-

376 HUMAN EMBKYOLOGT.

fication in these latter tarsal bones and in the sesamoid bones and
the various epiphyses appears after birth. In the talus, according
to Sewell (1906), dark-staining regions in the hyaline cartilage
of which it is composed in the sixth fetal month indicate structural

B

i ^

Fio. 203.— (AfMr R. Quain, Quain's
the bona of (he foot. A. Right foot or a
digital phHJsnge< an owHlied. The Uraus i
caneus. B. Fetus o( 7-8 monthe. Nurleit
y«r. Nucleus in third cuDeiform. E. Ii

G. About the age ol puijerty,

calcaueua. Epiphyees of meta

caneusi 1', in G, the epiphyMs of the caleaneu

10th ed.

vol. ii, Pt.

month.-.

The shafts

o( the melatanal boaea ant

omejcej

.1 birth. NuileuB i

1. D

•I the ■

nueloua o( the talun; 3, of the euboid :
. . . . uLar; 7. of thosecond ouneiform; S, metAlanal bones;

8'. distal epiphysis of llie senmd metatarsal bone; S" p^o^i^lBl etiiphysis of the first metBtanal bone ; 9,
first phalanx of Ihe second toe; 9', proximal epiphysifi of this phalanx; 9*, (hat of the first phalanx of th«
ereiit U>9 ; 10. second phalanx; 10'. the ^pbysis of tliie phalanx; 10*, epiphysia of the terminal phalanx
of the great toe : 11. terroiDal phalanx; 11 ', iu epiphysis.

features characteristic of the adult bone. The following tables
and the accompanying figures illustrate the process of ossification
in the inferior extremity. Authors differ in the data which they
give concerning the time of ossification of the various bones. When
not otherwise indicated the tenth edition of Quain 's Anatomy is
followed in the tables.

MORPHOGENESIS OF THE SKELETAL SYSTEM.

377

TABLE OF OSSIFICATION OF THE BONES OF THE INFERIOR EXTREMITY.

(Days and weeks refer to the prenatal, years to the postnatal period.)

Bone.

Centres.

Time of appearance
of centre.

Os COX2B Os ilium 56th day (Mall)

Femur

Os ischii

Os pubis

Os acetabuli.

Epiphyses:
Those of the acetab-
ulum

Crest of ilium

Tuberosity of isch-
ium

Patella
Tibia . .

Ischial spine

Ant. inf. spine of
ilium

Symphysis end of
OS pubis (1 or 2
centres)

Diaphysis

Epiphyses:

Distal end

Head

Great trochanter . . .

Small trochanter . .

FibuU.

Calcaneus

Diaphysis

Epiphyses:

Proximal end

Distal end

Tubercle (occas.)

Diaphysis

Epiphyses:
Distal end —
Proximal end.

Chief centre —

Epiphysis (distal end)

105th day (Mall)

4th to 5th fetal month

9th to 12th year

Soon after puberty

Soon after puberty. . .
Soon after puberty. . .

Soon after puberty. . .
Soon after puberty. . .

18th to 20th year.
(Sappey)

Time of fusion: general remarks.

The rami of the ischium and the pubis are
united by bone in the 7th or 8th year
(Ouain) ( 12-14 year^ Sappey). In the ace-
tabulum the three hip bones are separated
by a Y-shaped cartilage until after puber-
ty. In this cartilage between the ilium and
pubis the ' 'os acetabuli "appears betwe^i
the ninth and twelfth years. This bone,
variable in siae, forms a greater or less
part of the pubic portion of the articular
cavity. Leche (1884). Krause (1885), and
many others consider it primarily an in-
dependent bone. About puberty between
the ilium and ischium and over the ace-
tabular surfaces of these bones small ir-
regular epiphyseal centres appear. The
OS acetabuli becomes imited to the pubic
bone about puberty and soon afterwards
the acetabular portions of the ilium and
ischium and the ischium and pubis begin
to become united by bone. The acetab-
ular portions of the pubis and ilium are
unit^ a little later. Osseous union takes
place earlier on the pelvic than on the
articular surface of the acetabulum. The
imion of the several orimary centres and
the epiphyses is usuaJly completed about
the tw^itieth year.

Fuses with main bone 20th to 25th year.

Fusion begins in the 17th jrear and is com-
pleted between the 20th and 24th years
(Sappey).

18th to 20th year (Poirier).

18th to 20th year (Poirier).

After the 20th year.

43d day (Mall)

Shortlybefore birth.»« , 20th to 24th year.

Ist year 18th to 19th year.

3d to 4th year. (Osse- 18th year,
ous granules soon
afterbirth, Poirier) i

13th to 14th year ' 17th year (Quain).

8th year (Sappey) Proximal epiphysis 18th to 22d year

I (Poirier).

3d to 5th year The osseous patella reaches its definitive

form soon before puberty.
44th day (Mall).

About birth | 19th to 24th year (Sappey).

2d year 16th to 19th year.

13th year

65th day (Mall).

2d year

Fuses with epiphysis of the proximal end
and then with this to the diaphysis.

20th to 22d year.

3d to 5th year 22d to 24th year.

6th fetal month

10th year (Quain)

7th-8th year ( Sappey)

The chief nucleus is endochondral. A peri-
osteal nucleus appears frequently in the
4-5 fetal month (Hassel wander).

15th-16th year (Quain).

16th-18th year (Poirier).

(^ 17-21, average 20 years.

9 13-17, average 16 years (Hasselwander)

*• Poirier, Traite d'Anatomie, vol. 1. page 227, gives a summary of the literature on the time of the
appearance of this epiphysis. The epiphysis has some medico-legal importance, since its presence or
absence has been utilized to determine whether a child is bom at term. Schwegel found it to appear
between birth and the third year; Casper in the ninth fetal month. Hartmann found it lacking in 12 per
cent, of cases at birth and in 7 per cent, of cases present as early as the eighth fetal month.

378

HUMAN EMBRYOLOGY.

Bone.

TaluB.

Cuboid

Cuneiform III.
Cuneiform I...
Cuneiform II..
Navicular

Metatarsals .

Phalanges:
Terminal row

Middle row.

Proximal row

Centres.

Diaphjrsee
Epiphyses

Sesamoid bones
of the great
toe

Time of appearance
of coitre.

6th fetal month (Has-
sel wander).

About birth
1st year.
2d-3d year.
3d-4th year.
4th-5th year.

8th-10th week
3d-8th year....

Diaphyses

Epiphyses (distal)

Diaphyses

Epiphyses

Diaphyses

Epiphyses

58th day (Mall).

4th year

4th-10th fetal month
3d year ,

3d fetal month

3d year

cf 14th year

9 12th-13th year

Time of fusion: general remarks.

In the 7th-8th year the posterior part of
the talus, the os trigonum, is frequently
ossified from a special c«itre (v. Bardele-
ben). It fuses about the 18th year.

According to v. Bardeleben a second centre
of ossincation appears much later than
the primary in the navicular, and finally
about the time of puberty a medial epi-
physeal centre arises.

The centre for the 2d metatarsal usually
appears first, then come the 3rd, 4th, Ist
and 5th. The epiphysis of the 1st meta-
tarsal appears at the proximal end of the
bone: the other epiphyses arise at the
distal exida of the metatarsals. There may
be a distal epiphysis in the first meta-
tarsal also.17 In some instances a proximal
epiphysis is formed cm the tuberosity of the
fifth metatarsal (Gruber). The epiphyses
unite with the shafts in the 17-21 year
in males and in the 14-19 year in females.
(Hassd wander) .

cf 13-23, average 16-21 year.

9 13-17, average 14-17 year (Hasselwan-
der).

(5^ 15-19 year.

9 13-16 year (Hassel wander).

cf 15-17 year.

9 14-15 year (Hassel wander).

The centres for the shafts of the phalanges
often appear double, one for the dorsal
and one for the plantar surface. The
centres for the medial phalanges in each
row usually appear before the more later-
ally placed centres. The ooEitre for the
5th terminal phalanx appears much later
than the other centres in this row (Mall).
According to Rambaud and Renault the
epiphyses arise each from two centres
which fuse together. In the terminal
phalanx of the ^reat toe the ossification
centre of the epiphysis often appears as
early as the secona or even the first year.
(Hassel wander) .

Ossification may begin in the 8th year in
females, in the 11th in males (Hassel-
wander).

>^ Mayet has described two centres of ossification for the proximal epiphysis of the first metatarsal, one
of which represents the real metatarsal of the first digit.

MORPHOGENESIS OF THE SKELETAL SYSTEM. 379

Infantile Characteristics of the Skeleton of the Inferior Extremity.
— In the infant the pelvis is small in proportion to the size of the body and
contains a smaller proportion of the abdomino-pelvic viscera than in the adult.
The cavity of the infantile pelvis is cone-shaped and diminishes in diameter
from the entrance to the outlet (Fehling, 1876, Hennig, 1880). The blades of
the ilium are relatively slightly developed. In the first half of fetal life the
sacropelvic angle is similar to that of quadrupeds, but during the latter half
and after birth the angle becomes greater, expanding from 55** to 90-110" in
the adult (Le Damany)."

The acetabulum is relatively shallow in the new-bom as compared with the
adult. The shafts of the long bones are relatively shorter and thicker. The neck
of the femur is but slightly developed at birth. The infantile foot has certain
ape-like characteristics and is strongly flexed and inverted. The head of the talus
is directed more medialwards than in the adult, the first metatarsal is relatively
short and inclined medialwards by the oblique articular surface of the first
cuneiform (Leboucq, 1882).

SUPERIOR EXTREMITY.

Blastemal and Cnoij^DROGENOUS Periods.

In general the development of the superior extremity resem-
bles that of the inferior extremity. The various stages of differ-
entiation begin in the former a little earlier than in the latter.
W. H. Lewis (1902) has described the earlier stages in the develop-
ment of the arm. His description is closely followed here.

In an embryo at the end of the fourth week the scleroblastema
of the limb bud is marked by a slight condensation of the tissue
near the future head of the humerus. Early in the fifth week this
condensation has extended to the distal part of the limb bud and
the anlages of the scapula, humerus, radius, and ulna are distin-
guishable (see Fig. 294). The skeleton of the wrist and hand is
marked by a plate of condensed tissue. There are no distinct cen-
tres of chondrification at this stage.

In an 11 mm. embryo marked alterations have taken place in
the skeleton of the superior extremity (Fig. 295). Centres of
chondrification appear.

The scapula is composed of precartilage surrounded by a
dense blastema. It lies opposite the lower four cervical and the
first one or two thoracic vertebrae. From the superior border there
springs a large curved acromion process. On the medial (costal)
surface, at the junction of the humerus with the scapula, arises a
large hooked coracoid process. A slight ridge on the medial sur-
face marks the future anterior border. The perichondrium is
well marked onlv on the medial surface.

The clavicle is an ill-defined mass of condensed tissue which
extends from the acromion about a third of the distance to the

u

For recent accounts of the development of the pelvis, see Merkel (1902)
and Falk (1908). Fehling recognized sexual differences in the pelvis early in
fetal life.

380 HUMAN EMBRYOLOGY.

tip of the first rib. The coracoclavicular ligament is partially
differentiated.

The humerus is short and thick. The shaft is composed of
embryonic cartilage surrounded by a dense layer of perichondrium.
Towards each end of the shaft the central tissue is precartilaginous
in character. The surrounding perichondrium is continued
directly into the dense tissue of the neighboring skeletal parts.

There is more flexion at the elbow than during the preceding
stage. The forearm is midway between supination and pronation.
The core of the shaft of each bone is composed of hyaline cartilage.

The hand-plate is composed of condensed mesenchyme. There
are several centres of increased condensation which probably cor-
respond to the carpal bones. The digits are marked by condensed
tissue in which no segmentation into metacarpals and phalanges is
visible.

In an embryo of 14 mm. the skeleton of the superior extremity
is well advanced in development (Fig. 296). The form of the
scapula is shown in this figure. It is composed mainly of cartilage,
covered by a thick layer of perichondrium. It has migrated
caudalwards so that less than one-half of it lies anterior to the
level of the first rib. The clavicle is a rod composed of dense
tissue. It extends from the acromion to the tip of the first rib,
where it is continued into the sternal anlage. It contains a small
core of a peculiar precartilaginous tissue. The acromioclavicular
ligament is distinct.

The humerus is larger and more slender than at the preceding
stage and has expanded at each end. It is composed chiefly of car-
tilage surrounded by a thick perichondrium which is continuous
with that of the lateral angle of the scapula. There are no signs
of a joint cavity at the shoulder.

The ulna and radius are likewise composed of cartilage sur-
rounded by a thick perichondrium continuous at one end with that
of the humerus and at the other with that of the wrist. There are
no joint cavities at the elbow.

The carpus is composed of a dense tissue in which are em-
bedded cartilages which represent the bones of the wrist with the
exception of the lunar and the pisiform. These are still composed
of condensed tissue.

The metacarpals are represented by five slender cartilages
surrounded by a dense perichondrium. The first metacarpal is
only about half the length of the others.

The phalanges of the first row, with the exception of that of
the thumb, have cartilaginous cores. The basal phalanx of the
thumb is composed of condensed tissue. At the tip of each digit
is a mass of condensed tissue. There are no joint cavities present
in the hand.

MORPHOGENESIS OP THE SKELETAL SYSTEM. 381

In an embryo 20 mm. long the cartilaginons anlages of various
bones of the superior extremity are all well marked, except those
of the distal row of the phalanges of the fingers. The clavicle
extends from the acromion to the sternum. It is composed of a
peculiar kind of precartitaginous tissue. The general shape of
the other cartilages may be seen from Fig. 297. The spine of the
scapula is not yet distinct. There are distinct coracoclavicular,
costoclavicular, and interclavicular ligaments. There is no joint

Magn. R : 1. Flu. 2Bn.— (AfU
im. emiir.vo. Magn. about 13 :

cavity at the shoulder, but a capsular and a coraeo-humeral liga-
ment may be distinguished. The humerus has well-marked tuber-
osities and condyles. The ulna and radius are larger and longer
than at the preceding stage. The olecranon, coracoid, and styloid
processes are composed of cartilage and condensed tissue. The
perichondrium about the ulna and radius is quite thick. The cap-
sular and annular ligaments are present, but there are no joint
cavities.

All the bones of the carpus have cartilaginous centres. There
are no joint cavities in the hand.

382 HUMAN EMBRYOLOGY.

During the third month of development the cartilages of the
superior extremity assume more and more the form characteristic
of the adult bones ; in several ossification begins ; the joint cavities
appear at this time.

The early development of the bones of the forearm and hand,
and especially those of the wrist, has engaged the attention of
several investigators. The following details are based upon the
recent paper of Graefenberg (1906).

FOBEAKM.

The form and relations of the cartilaginous radius and ulna
in the fifth, sixth, and the seventh weeks of embryonic life are
shown in Figs. 298, 299, 300. The two cartilages are at first some
distance from one another. The proc. styloideus of the ulna begins
to develop during the latter part of the second month. It extends
at first to the dorsal side of the triquetrum and becomes relatively
large. Later the process becomes smaller, and is carried proxi-
mally and volarwards.

The discus articularis arises from a mass of tissue which lies
between the radius and the styloid process of the ulna. This mass
of tissue gives rise to a special centre of chondrification, which
by some is supposed to represent the os intermedium antebrachii
of the lower vertebrates.

THE CARPUS.

Os Centrale. — Most of those who have studied the develop-
ment of the human carpus have described a cartilage which is
homologous with the os centrale of the carpus of lower vertebrates.
The position of this element is shown in Figs. 298, 299, and 300.
It later disappears. In the process of retrograde metamorphosis
it may become divided into several parts. According to Graefen-
berg it does not fuse with any of the other carpalia.

The Proximal Row or Bones. — The navicular arises from
two centres of chondrification. It is homologous with the radiale
of lower forms. The lunar is the last of the carpalia to be differ-
entiated. According to Gegengaur and some other investigators,
it is homologous with the os intermedium of the lower vertebrates.
In man, however, there are no indications of its wandering from
the forearm into the wrist. The triquetrum is relatively small
when first differentiated, but grows rapidly in size (Figs. 298, 299
and 300). Perna has found it arising from two centres of chondri-
fication. The pisiform is relatively large in embryonic stages. It
is a canonic carpal element and not a sesamoid bone. It arises
later than the triquetrum. During its development it wanders
from the ulnar margin to the volar surface of the triquetrum.

MORPHOGENESIS OP THE SKELETAL SYSTEM. 383

The Distal Row. — The cartilages of the distal row are at
first relatively large compared with those of the proximal row

J. AnBlomiMhe Hefte, IBOO, Fi«. 1.) Dorml view of ■ model of th»
le forearm and hand of * Gve-weeks human onbryo. Magn. TO : I.

jf ibe skeleton of the forcann and hand of a

liniu; the cmtmla betwe

atum; »un.. humerus; M.mo)'., multaii(ulun
., pare radialit, ubt., i»r« ulnaris : P., pisiforme ;
The oafwtatum Um betweeo tha bunatum and the muKanpi

Fio. 300.— A. (After Gr^fenberc, 1906. Pig. G.)
ekelelOD of the right hand of a ten-weeks human fetua.

(Figs. 298 and 300). The capitatum is the largest, next comes the
hamatum. The multangalar carpalia are small; the M. majus is
for a time considerably smaller than the M. minus. The capitatum

3d4 HUilAX EJIBRYOLOGY.

and hamatum are the first elements of the carpus to undergo
chondrification. The hamulus ossis hamati is differentiated from
a special centre of chondrification.

urn tuid hsmBtum. B. Elbow-joint of a fetui
c. centnl udLdq: d, perichoadr*! put of Juia
anoa. D, £, F. Should er-joiat o[ a fetua 13
m of mpiiulei t. intracepsuUr eonnwtive tiMi

Anat. Abt., 1879.) Fir
diocarpflj ioiut in thrc«

Metocarpalia. — These are at first relatively large. The first
metacarpal, according to some investigators, represents a basal
phalanx. Galen was the first to express the view that the meta-

MORPHOGENESIS OF THE SKELETAL SYSTEM.

385

carpal of the thumb is not present. Others have thought that a
phalanx is missing from the thumb, but Graefenberg accepts the
view of Galen. The other four cartilaginous metacarpals arise
at some distance from one another (Fig. 298). They spread apart
distally. The bases are first brought into contact with one another,
and later the distal ends. The fifth metacarpal articulates at
first with the triquetrum (Fig. 298) and later with the hamatum
(Fig. 299).

The phalanges are differentiated in serial order, the basal
row appearing first, the terminal row last. According to Graefen-
berg, the terminal phalanges show evi-
dence of being composed of two ele-
ments, a proximal and a^ distal. The
latter is composed of cartilage, the cells
of which rapidly enlarge. It may repre-
sent a fourth phalanx. Primitively the
digits were probably composed of many
phalanges. The terminal phalanges are
at first smaller than those of the middle
row, but then develop faster so as to exceed them in length. After
a time retrograde metamorphosis overtakes the distal ends of the
terminal phalanges, so that the middle row once more exceeds
the terminal in length. The tuberositas unguicularis is composed
of fibrous tissue which becomes transformed directly into bone.

The sesamoid bones, according to Thilenius, are more numer-
ous in the fetus than in the adult. The following table, after
Pfitzner and cited by Dwight (1907) illustrates this. This table
is based on a study by Thilenius of 30 hands of fetuses of the
fourth month, and of 1440 hands by Pfitzner of individuals from
fourteen to eighty-nine years of age. The Roman numerals indi-
cate the metacarpophalangeal joints opposite which sesamoid
bones were found, and the Arabic numerals represent the per-
centage of frequency with which the bones were found.

Fio. 302. (After R. Qiiain, Qtiain's
Anatomy, 10th ed., vol. ii, Pt. 1, Fig.
1 15.) Ossification of the clavicle. A.
Clavicle at birth. B. At about the
twenty-third year. 1, shaft; 2, epiph-
yma.

I.

R.

Embryos
Adults . . .

(100
(99.9

L.

II.

R.

100)
100)

(46
(48

23)
0.1)

III.

R.

(30

(1.4

L.

15)
0)

IV.

R.

(23

(0

L.

36)
0.1)

V.

R.

(8
(2.1

84)
82.5)

JOINTS.

Schulin (1879) has given some account of the development of
the joints of the upper extremity.

At the shoulder- joint (Fig. 301, D, E, F) a joint fissure arises
in the periphery of the intermediate zone and thence extends

Vol. I.— 25

386 HUMAN EMBRYOLOGY.

inwards between the head of the humerus and the glenoid fossa
(Fig. 301, D). The joint cavity extends into the perichondrium
for some distance on each side of the head of the humerus, so that

* c

Fio, 303.—

A. B

C. D. A(M

r R

Quain. Quun's Ai

Alter Sappcy, T

Fi(. 1*5.) 0»ific

15 or 16 1-™™.

C, A

17 or IS

9. D. At 22 y«r(

Ep..

opiphy>ia.

E

Epiphyw. of ™p

, in

body

f the Rop

ll.-.

6. cirtilMB betweei

epiphyn-ofacro

. cwtilwn

out border of «(«pul>i 1

in cartiUgiDOUB

Kirde'r

ol KspuU

i. Pt. I. Fig. lis. 1
mioD; Cur,, centre i

R. Quain

y«r. C. At 3 years. D. Atfiyean'. E. At 12 years. F. At puberty

hffld; 3

medial part of tronhles; 7, nucleus of lateral epipondyle.

there is from a very early period a well-developed layer of intra-
capsular connective tissue (6). The labrum glenoidale is differ-
entiated at an early period. After the joint cavity appears the

MORPHOGENESIS OF THE SKELETAL SYSTEM.

387

head of the humerus undergoes considerable development. (Com-
pare D, E, F, Fig. 301.) During fetal development the tendon of
the long head of the biceps sinks in through the capsule of the

Fig. 306.

Fia8. 305 and 306. — (After R. Quain, Quain's Anatomy, 10th ed., vol. ii, Pt. I, Figs. 119 and 120.)
Ossification of the radius and uhia. Fig. 305. Radius. A. At term. B. At 2 years. C. At 5 years.
D. At 18 years. Fig. 306. Ulna. A. At birth. B. At the end of the fourth year. C. At 12 years.
D. At 19 to 20 years. Ep., epiphysis.

joint. For a time it is covered by a layer of synovial membrane
which attaches it to the capsule, but in the third or fourth month
it becomes free in the joint cavity (Welcker, 1878).

The elbow- joint (Fig. 301, B and C) develops in a position
of flexion at about 90°. The perichondral part of the joint cavity

388 HUMAN EMBRYOLOGY.

<Fig. 301, B, d) develops before the intercartilaginous part. The
distal end of the humerus undergoes marked alterations in form
during the development of the joint (Fig. 301, C).

In the wris1>joiiit cavities appear during the third month
(Fig. 301, A). At the radiocarpal joint the joint cavity arises from
three separate fissures (&).

Frn, 807.— <Aftar R. Quiin, Quwn'n Anatomy. 10th ed., vol, ii. Pt. I. Tie. 121.) OniGcatioD of
the bODB at Ihe liMid. A. At birth. The carpus is cBrti1««inous. The thiLla of the metacarpals and
phalanflee are oeaified. B. At the ead of the first /ear. C. About the third year, D. At the iifth year.
E. At the ninth year. 1, csapitaCum; 2, hamatum; 3, triquetrum; 4, lunatuin; 5. multangulum loajus;
6, navicular; 7. multanAulum minus; 8, metacarpal shafts; 8*. four maCacarpalepiphyBce; 8', tHatof the
thumbs 0. boasl phalanges; 9*, tbeii epiphyses; 9'. that of the thumb; 10. [Diddle pholaosea; 10', epiph-
ysisof (erminal phalaUTt of thumb; It, terminal phalanflee of the fingers; 11*, their epiphysca.

The development of the digital joints has been previously
described (Figs. 226-228).

Period op Ossification.

With the exception of the clavicle the bones of the superior
extremity pass through a stage of embryonic hyaline cartilage
before becoming ossified. The shaft of the clavicle, which is the
first bone in the body to exhibit a centre of ossification, is ossified

MORPHOGENESIS OP THE SKELETAL SYSTEM.

389

in a peculiar kind of cartilage (Mall). The ends of tbis bone exhibit
the more usual type of ossific cartilage. The following table
gives the approximate periods when the various centres of ossi-
fication appear and the time of fusion of the various centres
which unite to form the individual bones. Authors differ con-
siderably concerning these data. When not otherwise indicated,
the data included in this table are based upon those given in
Quain's Anatomy, 10th edition, vol. 2, p. 106.

According to Pry or (1906), the epiphyses of the hand appear
earlier and unite to the shaft earlier in females than in males a|>d
in the first-bom children earlier than in those bom later. **The
fully developed hand of the female is at least two years in advance
of the male.^^ Similar conditions have been found by Hassel-
wander in the skeleton of the foot.

TABLE OF OSSIFICATION OF THE BONES OF THE SUPERIOR EXTREMITY.

(DtLYB and we^s refer to the prenatal, years to the postnatal period.)

Bone.

Clavicle

Scapula

Centres.

Diaphysis

Sternal epiphysis.

Time of appearance of
centre.

Primary centres:

1. That of the body, the
spine, and the base of
the glenoid cavity.

2. Goraooid process

3. Subcoraooid

Himierus .

Epiphyses:

Acromial epiphyses

Epiphysis of the infe-
rior angle.

Epiphyses of the verte-
bral border.

Epiphjrses of upper sur-
face of coracoid.

Epiphysis of surface of
glenoid fossa.

Diaphysis

Epiphyses:

Head

Tuberculum majus . . .

Tuberculum minus

Capitulum

Epioondylus med

Lateral margin of troch-
lea.

E|Hcondylus lat

6th week

18th to 20th year.

Union of primary and second-
ary centres; remarks.

8th week (Mall).>*

1st year.

10th to 12th year.

15th to 18th year.
16 to 18th year.

18th to 20th year.

16th to 18th year.

16th to 18th year.

6th to 7th week (Mall)

1st to 2d year.
2d to 3d year.
3d to 5th year.
2d to 3d year.
5th to 8th year.
11th to 12th year.

12th to 14th year.

There are two centres in the
shaft, a medial and a lateral.
These blend on the 45th day
(Mall). Shaft and epiohysis
unite between the 20tn and
25th years.

The chief centre appears near
the lateral angle. The sub-
coracoid centre appears at
the base of the coracoid proc-
ess and also gives rise to a
part of the superior mar|^ of
the glenoid fossa. The cora-
coid process joins the body
about the age of puberty. The
acromial epiphjrsMtl centres
(two or three in number) fuse
with one another so(m after
their u>pearance and with the
spine between the 22d and
25th years ((jjuain); 20th
3rear (Wilms). The subcora-
coid and the epiphjrses of
the coracoid process, the i^e-
noid fossa, the inferior anjB^e,
and the vertebral margin join
between the 18th and 24th
years in the order mentioned
(Sappey).

The epiphyses of the head, the
tuberculum majus Bnd the tu-
berculum minus (the last is
inconstant) imite with one
another in 4th-6th srear and
with the shaft in 20th-25th
year. The epiphyses of the
capitulum, lateral epicondyle,
and trochlea unite with one
another snd then in the 16th~
17th year join the shaft. The
epiphysis of the medial epicon-
dyfe joins the shaft in the
18th year.

1* According to Poirier, Traitd d'Anatomie, p. 138, two centres appear in the eighth week, and unite
in the third month to form a centre of ossification for the body of the scapula.

390

HUMAN EMBRYOLOGY.

Bone.

Radius

Ulna

Carpus

Metacarpals ,

Centres.

Phalanges

First row —

Middle row..

Diapbysis ,

Epiphyses:
Carpal end

Humeral end

Diaphysis

Epiphyses:
Carpal end

Humeral end

Os capitatum

Os hamatum

Os triquetrum

Oslunatum

Os naviculare

Os mult, maj

Osmult. min

Os pisiforme

Diaphsrses

Proximal epiphysis of
the first metacarpal

Distal epiphyses of
the metacarpals.

Time of appearance
of centre.

7th week (Mall)

9 8th month,

cT 1 6th month (Pryor),

6th-7th year.

7th week.

9 6th-7th year.

(^ 7th-«th year ( Pryor

loth year.

Diaphyses

Proximal epiphyses . .

93d-6th month

(^ 4th-10th month.
V5th-10th month.
^ 6th-12th month.
9 2d-3d year.
cT about 3 yean,
93rd-4thyear.
(^ about 4 years.
Vat 4 years, or early

in 5th year.
d about 5 years.
94th-5thyear.
(5'6th-6thyear.
94th-5thyear
(f 6tn-6th year.
99th-10thyear.
cT 12th-l3th year.

9th week (Mall)

3d year.
2d year.

9th week (Mall)

l8t-3d year (Pryor).

Terminal row

Diaphyses

Proximal epiphyses . .

Diaphyses

Proximal epiphyses .

Sesamoid bones

llth-12thweek(Mall)
2d-3d year.

7th-8th week.
2d-3d year.

Union of primary and secondary
centres; remarks.

The superior epiphysis and shaft unite be-
tween the 17th and 20th years. The in-
ferior epiphysis and shaft about the 21st
year (Pryor); 921st year, cf2l8t-25th
year (Sappey). Sometimes an epiphysis
IS found m the tuberosity (R. and K.)
and in the styloid process (Sappey).

The centre for the shaft of the ulna arises
a few days later than that for the radius.
The proximal epiphysis is united to the
shaft about the 17th year; the inferior epi-
physis between the 18th and 20th years;
9 20th 7 21st years, cf 21st -24th years
(Sappey) . There is sometimes an epiphy-
sis in the styloid process (Sohwegel) and in
the tip of the olecranon process (Sappey).

The navicular sometimes has two centres
of o.osification (Serres. Rambaud and
Renault). Serres uid Pryor have de-
scribed two centres of ossification in the
lunatum. Debierre has described two
centres in the pisiform, one in a girl of
eleven, the other in a boy of twelve. The
OS hamatum may have a special centre
for the hamular process. Pryor has
found two centres in the triquetrum.
Pryor (1908), describes the centres of
ossification of the carpal bones as assum-
ing shapes characteristic of each bcme at
an early period.

The centres for the shafts of the seccmd
and third metacarpals are the first to
appear. There may be a distal epiphysis
for the first metacarpal and a proximal
epiphysis for the second. Pryor (1906).
found the distal epiphysis of the first
metacarpal in about 6 per cent, of cases.
It is a family characteristic. It arises be-
fore the 4th year and unites later. Pryor
found the proximal epiphysis of the second
metacarpal in six out of two hundred
families. It unites with the shaft between
the 4th and 6th-7th year; sometimes,
however, not until the 14th year. In
the seal and some other animals all the
metacarpals have proximal and distal
epiphyses (Quain). The epiphyses join the
shafts between the 15th and 20th years.
There may bean independentepiphysis for
the styloid process of the 5th metacarpcd.
The epiphysis of the metacarpal of the in-
dex finger appears first. This is followed
by those of the 3d, 4th, 5th, and 1st digits.

The shafts of the phalanges of the second
and third fingers are the first to show
centres of ossification. The phalanges of
the little finf^er are the last, ^he epiphy-
sis in the middle finger is the first to ap-
pear. This is followed by those of the
4th, 2d, 5th, and 1st digits.

The centres in the shafts of this row are
the last to appear. The epiphysis of the
phalanx of the middle finger is the first
to appear. This is followed by thof«e of
the ring, index, and little finger (Pryor).

The terminal phalanx of the thumb is the
first to show a centre of ossification in
the shaft. This is the first centre of ossi-
fication in the hand. It is developed in
connecti ve tissue while the centres of the
other phalanges are developed in carti-
lage (Mall). The epiphysis of the ungual
phalanx of the thumb is followed by those
of the middle, ring, index, uid littlenngers.
The fusion of the epiphyses of the pha-
langes with the diaphyses takes place in
the 18th-20th year.

Ossification begins generally in the 13th-
14th years, and may not take place until
after middle life (Thilenius). For table
of relative frequency in the embryo and
adult see p. 385.

MORPHOGENESIS OP THE SKELETAL SYSTEM. 391

BIBLIOGRAPHY.

(On the development of the skeleton of the extremities in man. A few recent
articles on variations and congenital deformities are included.)

Adrian, C: Uber kongenitale Humerus- und Femurdefekte. Beitrage zur klin.

Chir. Bd. 30. 1901.
Alexander, Bela: Die Entwicklung des knochemen Handskelettes vom Beginn

der ersten Knochenpunkte. Wiener klin-therap. Wochenschrift Nr. 27-28.

1905.
Die Entwicklung des menschlichen Handskeletts. Arch, fiir physikal. Med.

Bd. 1. 1906.
Alsberg, M. : Die statisch-mechanischen Prinzipien der Extremitatenbildung beim

Menschen und bei den Festlandtieren. Polit. Anthropol. Revue. Bd. 5,

S. 605-6n. 1907.
Anthony, R.: L'^volution du pied humain. Bull, et Mem. Soc. d'Anthrop.

Ser. 5, T. 3, p. 818-835. Paris 1903.
Rev. Scientif. Ser. 4, T. 19, p. 129-139. 1903. Transl. in Annual Report

of the Smithsonian Institution, p. 519-535. 1904.
Appraill^, G. : Malformations cong^nitales de I'extremite superieure du radius.

Thhse. Paris 1901.
Bade, P.: Die Entwicklung der menschlichen Fussknochen nach Rontgogrammen.

Sitz. Ber. Niederrhein. Ges. Bonn 1896.
Die Entwicklung des menschlichen Skeletts bis zur Geburt. Arch. mikr.

Anat. Bd. 55. 1899.
Entwicklung des menschlichen Fussskeletts von der neunten Embryonalwoche

bis zum 18. Jahre nach Rontgenbildem. Verb. d. Gesellsch. deutscher

Naturf. und Arzte. S. 463-466. 1899-1900.
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Wright, William: Case of Accessory Patellae in the Human Subject, with Re-
marks on Emargination of the Patella. Joum. of Anat. and Physiol. Vol.
38. 1903.

WuTH, E. A.: Uber angeborenen Mangel sowie Herkunft und Zweck der Knie-
scheibe. Arch. klin. Chir. Bd. 58. 1899.

398 HUMAN EMBRYOLOGY.

E. THE SKULL, HYOID BONE, AND LARYNX.

General. Features.

We may distinguish in the skull, considered purely topo-
graphically, a neural and a visceral region. The neural region
serves to protect and support the brain and sense organs; the
visceral, for the alimentary and respiratory tracts. A sharp
demarcation between the two regions is not possible. Thus the
base of the skull, especially its axial portion, has relations to both
regions, and through change of function changes in the two regions
may be brought about (ear ossicles). We shall begin with a
description of the axial part of the skull, which generally is counted
a part of the neural region.

The axial region is that portion which is continued forward
from the vertebral axis. It includes the basal portion of the occipi-
tal bone and the body of the sphenoid. In the embryo the chorda
dorsalis extends anteriorly to the hypophysis. The axial region
of the skull is thus divisible into chordal and prechordal portions,
the former lying posterior, the latter anterior to the hypophysis.
The chordal portion, is further divisible into an otic part, which
corresponds roughly with that portion of the base of the skull
which articulates with the temporal bone, and a postotic part,
which extends to the otic part from the spinal column. The pre-
chordal region supports the orbitotemporal and ethmoidal por-
tions of the skull.

The neural region lies dorsal, lateral, and apical from the
axial region with which it is intimately associated. It serves to
encapsulate the brain (cranial cavity) and the organs for hearing,
smell, and vision (petrous portion of the temporal bone, orbital and
nasal cavities).

The visceral region lies chiefly ventral and ventrolateral to
the axial region. In part it is closely associated with the neural
region. It includes the pterygoid processes of the sphenoid, the
hard palate, the bones of the upper and lower jaws, and the hyoid
bone. From the primitive visceral skeleton of the head are also
derived the bones of the middle ear and the cartilages of the
larynx.

In the development of the complex skeletal apparatus of the
head, overlapping blastemal or membranous, chondrogenous, and
osseogenous stages may be distinguished.

The origin of the mesenchyme of the head has already been
described (p. 297). It is at first rather loose in structure, but soon
becomes condensed in various regions. This condensation usually
marks the beginning of the differentiation of the mesenchjine into
muscles and into various connective-tissue structures of more or

MORPHOGENESIS OP THE SKELETAL SYSTEM. 399

less definite form, tendons, fascias, dermis, submucous coats, mem-
branes of the brain, and portions of the organs of special sense
and the anlages of the skull and the larynx. The membranous
anlage of the skeleton of the head is gradually developed from
several centres of condensation. In part it is transformed into
cartilage, forming the chondrocranium.

The chondrocranium arises through the fusion of a consider-
able number of cartilages which originate from independent
centres of chondrification. Some of these centres of chondrifica-
tion arise in mesenchymatous tissue which shows no well-marked
condensation preceding the formation of cartilage. The trans-
formation of membranous tissue into cartilage in some instances
takes place very rapidly, in other instances slowly.

The chondrocranium reaches its highest relative development
in the third month of intra-uterine life. At this period it com-
prises the axial region of the skull, the auditory and olfactory
capsules, the orbital wings and the bases of the temporal wings of
the sphenoid, the occipital condyles, and the tectum posterius
which lies dorsolateral to the occipital and temporal regions (Figs.
312 and 313). In the first and second branchial arches well-marked
cartilaginous skeletal structures are formed ; in the first the mal-
leus and incus; in the second, the stapes and the styloid process
of the temporal bone. Ventrally the second, third, fourth, and
fifth branchial arches give origin to a cartilaginous hyoid bone and
to some of the cartilages of the larynx.

Ossification begins during the second month in man. The
skeleton of the head at this period, with the exception of the
chondrocranium described above, is composed of membranous
tissue. Ossification takes place in part directly in the membranous
tissue of the skull, in part in the chondrocranium.

Most of the individual bones of the human skull arise from
two or more centres of ossification, and many of them are partly
membranous, partly cartilaginous in origin. Neither the centres
of ossification nor the bones developed from them correspond very
perfectly with the centres of chondrification from which the
chondrocranium arises.

The chondrocranium is mainly, but not completely, replaced
by bone. The cartilages of the septum and alse of the nose, and
the fibrocartilago basalis, for instance, represent remnants of the
chondrocranium. Parts of the primitive cartilaginous skeleton
are converted into fibrous tissue instead of into bone. The stylo-
hyoid ligament is an example of this.

Gaupp has shown that the cavum cranii of mammals is not quite homologous
with that of reptiles. On each side there lies a space, the cavum epitericum, above
the ala temporalis, which in reptiles is outside of and in mammals forms a part
of the cranial cavity (Mead, 1909, Voit, 1909).

400 HUMAN EMBRYOLOGY.

We may now consider the more important stages in the devel-
opment of the skull in somewhat greater detail.

Blastemaxi Period.

At the end of the second week of intra-uterine development
the chorda dorsalis extends to the dorsal margin of the bucco-
pharyngeal membrane (Fig. 229). On each side of it mesenchyme
fills in the space between the brain, pharynx, and ectoderm. As
the head develops the mesenchyme increases in amount. It extends
dorsally and apicalward so as to surround completely the brain
and its appendages. When the flexures of the brain appear,
mesenchyme extends into the fissures between the various seg-
ments of the neural tube. An especially large fold of mesenchyme
Mittelhirnpolster) is formed beneath the midbrain flexure (Fig.
266). The chorda dorsalis for a time remains attached to the
ectoderm of the caudal wall of the hypophyseal pocket, then loses
this connection and terminates free in the tissue immediately
behind the hypophysis beneath the midbrain flexure.

Toward iiie end of the fourth week the post-otic portion of
the axial region of the skull becomes marked by a condensation of
mesenchyme. This condensed tissue or *' occipital plate'' is not
sharply outlined. It consists of a blastemal central portion with
two lateral processes on each side, a caudal rod-like ** neural"
process and a flat apical process (see Fig. 231). Between these
two processes run the roots of the hypoglossal nerve. The chorda
dorsalis, surrounded by a perichordal sheath, lies in the sagittal
axis of the plate. At this period it may still be united to the
epithelium of the pharyngeal vault.

It has been previously pointed out that the post-otic axial
region of the manamalian head may be considered to be composed
of at least three segments comparable to the spinal segments.
This segmentation is best marked by the myotomes which develop
in the lateral portions of these segments. That part of the occi-
pital plate which lies in the most distal of the segments resembles
in some respects a spinal sclerotome tsee p. 334).

The apical end of the occipital plate extends into a thin layer
of dense tissue which surrounds the dorsal portion of the pharynx.
The chorda dorsalis extends forward in this tissue nearly to the
hypophysis. The tissue in which the chorda runs becomes much
thicker near the hypophysis than where it lies opposite the otic
labyrinth. The latter is surrounded by a layer of condensed tissue
connected for a short distance with the retropharyngeal tissue.

The mesenchyme in the visceral region of the head is much
condensed, but as yet no skeletal structures are definitely
outlined.

MORPHOGENESIS OP THE SKELETAL SYSTEM. 401

The chorda dorealis is composed of densely packed cells sur-
rounded by a very faint sheath. Outside of the chordal sheath
there is a weU-marked layer of mesenchyme cells or perichordal
membrane. In the region of the spine and of the occipital plate a
space is seen between the chordal sheath and the perichordal
membrane. This space is not seen apical to the occipital plate.

During the early part of the second month the membranous
anlage of the skull becomes extensively developed.

Fia. 308.— (After Q. Levi, Arch. f. mikr. Anst. u. EDdrickliuwefchinble, 1900, vol. Iv, Fir. t.) Mem-

The anterior and posterior lateral processes of the occipital
plate become united lateral to the hypoglossal nerve, so that the
hypoglossal foramen is completed and the membranous pars
lateralis of the occipital is formed. This pars lateralis is con-
tinued into the membranous vault of the skull, the origin of which
is described below.

The condensed tissue of the post-hypophyseal region increases
in amount and extends about the hypophyseal pocket into the
region apical from this, thus completing the anlage of the body
of the sphenoid {Fig. 308). This gives rise to orbitotemporal and
ethmoidal processes.

The orbitotemporal process is first marked by a mass of dense
mesenchyme which extends ventrolaterally toward the ectoderm

Vol. I.— 26

402 HUMAN EMBRYOLOGY.

caudal to the optic cup. It is connected with dense tissue which
surrounds tlie anlage of the orbit and with the anlages of the
membranous fioor and vault of the skull. In it are developed the
orbital and temporal wings of the sphenoid, the origin of which
will be described in connection with the chondroeranium. The
ethmoidal process extends anteriorly in the median line from the
anlage of the body of the sphenoid into the region between the
nasal fosste. It forms the anlage of the nasal septum and gives
rise to parts of the membranous floor of the cranial cavity and the
roof of the mouth (Fig. 310).

Fia. aOS.— {After C. Levi, Arch. t. mikr. Anat. u. EDt1rickluii(>B.. IBOO. vol. Iv, fl«. 2.) Skull of u
embryo 14 mm, long.

The tissue of the capsules of the lahjTinth increases in amount
as the labyrinth becomes differentiated. The tissue which encloses
the region of the semicircular canals and the vestibule forms an
oval mass the outlines of which do not conform to that of the
enclosed canals (Fig. 309). This tissue is less dense than most
I)art9 of the membranous skeleton of the head and at an early
period becomes transformed into embryonic cartilage (see p. 407).
The cochlear portion of the labyrinth (Fig. 310) is enclosed by a
dense mesenchyme which becomes converted into cartilage at a
later period.

lateral from the nasal fossa the tissue becomes generally
somewhat condensed, though less so than the tissue in the septum.
In the perinasal tissue condensation gradually marks out the
lateral and ventral portions of the nasal capsule and the mem-
branous floor of the ethmoidal and orbital portions of the cranial

MORPHOGENESIS OF THE SKELETAL SYSTEM. 403

cavity (Fig. 310). From the lateral wall membranous processes
project into the nasal fossa. These are the anlages of the concha?.

The floor of the cranial cavity at this period is formed pos-
teriorly by the occipital plate with its lateral processes and by
the capsule of the labyrinth. Between the two is a fissure for the
passage of the glossopharjTigeus, vagus, and spinal accessory
nerves and the jugular vein (Fig. 309). Apically the floor is
formed by a thin sheet of condensed tissue, which is slightly
marked over the ethmoidal region where the olfactory nerve
passes through it and is better marked on the anterior medial por-
tion of the roof of the orbit. This portion is connected caudally
with the orbital wing of the sphenoid (Fig. 310).

Between the orbital region and the capsule of the labyrinth,
in the vicinity of the Gasserian ganglion, the floor of the cranial
cavity is incomplete. More medially the floor of the cranial cavity
is formed by two membranes, one of which arises from the anterior
margin of the auditory capsule and the neighboring part of the
body of the sphenoid, and the other from the posterior margin
of the orbital wing of the sphenoid. These two membranes extend
upwards into the midbrain fold, fuse, and furnish a short central
skeletal support for the mesenchyme in this fold (Fig. 266). They
enclose the lateral process of Rathke's pocket. They form no part
of the definitive skeleton.

The roof of the cranial cavity is formed by a dense membranous
layer which first becomes marked at the side of the head in embryos
9-11 mm. in length. At this stage there is a plate of dense tissue
formed between the caudolateral margin of the orbit and the caudal
lateral process of the occipital plate. It lies lateral to the Gas-
serian ganglion and the capsule of the labyrinth, with the latter
of which it comes in contact. Below it is connected with the
orbitotemporal process and the dense tissue of the region of the
branchial clefts.

This membrane gradually extends so that it forms a complete
membranous vault. Ventrally it is continuous with the ventro-
lateral margin of the membranous covering of the ethmoidal and
orbital portions of the floor of the cranial cavity. Laterally it
becomes connected with the temporal wing of the sphenoid, the
auditory capsule, and the lateral part of the occipital. Caudally
it is continued into the much thinner membrana reuniens dorsalis
of the spinal canal.

During the period under consideration the brain only par-
tially fills the cranial cavity. A large amount of loose mesenchyme
intervenes between the brain and the floor and vault of the cranial
cavity. This tissue is especially abundant in the region of the
flexures of the brain and about the hemispheres (Fig. 266). In it

404 HUMAN EMBRYOLOGY.

the falx cerebri and other membranous supports of the brain are
developed. During the latter part of the second month an exten-
sive plexus of vessels develops on the cerebral side of the mem-
branous vault.

The anlages of the alveolar borders of the upper and lower
jaws become marked by condensation of tissue along the upper
and lower margins of the entrance into the oral cavity. This
condensed tissue at first forms a flat plate, but later sends proc-
esses in an aboral direction.

Chondrogenous Period.

A large amount of study has been devoted to the development
of the chondrocranium or primordial cranium in the different ver-
tebrates. An excellent summary of the chief literature on the
subject is given by Gaupp (1906). The chief work on the develop-
ment of the human chondrocranium has been done bv Dursv,
Spoendli, Hannover, Froriep, v. Noorden, Jacoby, O. Hertwig,
and Levi.

The development of the chondrocranium in man begins early
in the second month. Its relatively most complete differentiation
is reached toward the end of the third month, although some parts
of it undergo a still greater elaboration before conversion into
bone.

At the end of the third month (see Figs. 312 and 313) the
caudal half of the chondrocranium forms a ring of cartilage about
the posterior portion of the brain. The thick ventral portion of
this ring comprises medially the basilar portion of the occipital
and laterally the capsule of the labyrinth and the partes laterales
of the occipital. The dorsal portion of the ring is composed of
a thin plate of cartilage, the tectum posterius, the only part of the
cranial vault which becomes cartilaginous in man. In tlie partes
laterales of the occipital the hypoglossal foramina may be seen.
The processes which bound them anteriorly serve as the posterior
boundaries of the jugular foramina.

The caudal portion of the chondrocranium is united to the
apical portion by tlie relatively slender body of the sphenoid. At
the junction between the two is a large dorsum sellsB.

The apical portion from above appears somewhat quadrangu-
lar. The caudal angle of the quadrangle forms the body of the
sphenoid ; the apical angle, the ventral end of the nasal capsule ;
and the lateral angles, the tips of the alae orbitales of the sphenoid.
In the mid-line a well-developed nasal septum extends forward
from the body of the sphenoid. Seen from the side (Fig. 312)
the dorsal surface of the body of the sphenoid and the dorsal and
anterior margins of the nasal septum form three sides of a hemi-

MORPHOGENESIS OF THE SKELETAL SYSTEM. 405

hexagon. At the junction of the dorsal and anterior margins of
the nasal septum there is a prominent crista galli.

From the body of the sphenoid the temporal and orbital wings
project laterally. On each side of the dorsal margin of the nasal
septum there may be seen a quadrangular cribriform plate, the
lateral margins of which are united to the ala orbitalis by plates
of cartilage (cartilagines spheno-ethmoidales) which extend over
the orbit. There is also a plate of cartilage which extends to the
ala orbitalis from the dorsal surface of the axial region of the
chondrocranium near the junction of the sphenoidal and ethmoidal
regions.

The nasal fossae are bounded laterally by a plate of cartilage
which is united posteriorly to the anterior extremity of the body
of the sphenoid, dorsally to the lateral edge of the cribriform plate,
and anteriorly to the nasal septum. The inferior margin of this
lateral plate curves inwards, but does not extend to the nasal
septum. The inferior surface of the nasal fossa thus is not closed
off by cartilage. Anteriorly, however, the inferior aperture is
rendered very narrow by a paraseptal cartilage (see p. 413).
From the lateral nasal cartilage there arises a short process which
encircles a part of the nasolachrymal duct (processus paranasalis).

The orbit is bounded above by the orbital wing of the sphenoid
and the processes attached to this; posteriorly by the lateral
extremity of the ala temporalis, much of which has already become
ossified; and medially by the lateral nasal cartilage. The floor
and the lateral part of the roof of the orbit are formed of mem-
brane bone. At this period the parietal, frontal, nasal, and lachry-
mal bones, the maxilla, the ej^gomaticum and the squama tem-
poralis, the tympanicum, tlie laminae mediales of the pterygoid
process of the sphenoid, the vomer, and the palatine bones are
beginning to become ossified as membrane bones (see Fig. 321).

Those portions of the skeleton of the head derived from the
visceral arches are shown in Figs. 311, 312, and 314. From the
mandibular arch are derived MeckePs cartilage, the malleus, and
the incus. The malleus and incus have nearly their definitive
form, although relatively far greater in size than in the adult skull.
Meckel's cartilage, which is continued from the capitulum of the
malleus into the mandible, is a temporary structure which dis-
appears at a later period. It is at this time flanked by a mandible
formed of membrane bone.

The stapes, which at this period has its characteristic form,
and the styloid process of the temporal bone are derived from the
second branchial arch. The cartilaginous hyoid bone and the chief
laryngeal cartilages are clearly outlined, although the hyoid bone
is not thus represented in the model. These cartilages are derived
from the second, third, fourth, and fifth branchial arches.

406 HUMAN EMBRYOLOGY.

The skeleton of the rudimentary head of amphioxus is composed of the chorda
dorsalis, membranous tissue, and a few scattered structures, cartilaginous in charac-
ter. The cyclostomes have a rather complicated chondrocranium, the roof of which
is formed of membrane except for a slender tectum synoticum. The occipital region
is missing" and the cranium terminates caudally in the labyrinth region. Li selach-
ians the cranial cavity of the cartilaginous skull has a complete roof, side walls,
and floor, but is open in front and behind (f. magnum). In the vertebrates above
the selachians a chondrocranium is formed during embryonic development, but the
degree of its elaboration and the extent to which it is retained in the adult skull
vary greatly in the different classes of vertebrates. In the higher vertebrates the
chondrocranium is largely replaced by bone, partly of the investment (membra-
nous), partly of the substitution (cartilaginous) type. In man the chondrocranium
is relatively slightly developed and the investment bones are relatively extensive.

Having considered briefly the cartilaginous skeleton of the
head at the height of its development, we may now take up in
more detail the development of its component parts.

OCCIPITAL REGION, THE CAPSULE OF THE LABYRINTH, AND THE

TECTUM POSTERIUS.

Base and Partes Laterales of the Occipital. — ^A brief descrip-
tion of the development of the posterior part of the occipital
has already been given in connection with the description of the
cervical vertebrae. Early in the second month a centre of chon-
drification appears in the posterior part of the blastemal anlage
of the occipital on each side of the median line (Fig. 308).
Apparently a separate centre arises in the caudolateral (neural)
process, but this very quickly fuses with the main parachordal
centre, and it is possible that it is^. not always present.
Each parachordal cartilage ext.end^ loijward at the side of the
chorda dorsalis until the region is reached where the chorda
dorsalis enters the dense retropharyngeal mesenchyme. Here the
two parachordal plates fuse dorsal to the chorda into a single
median plate which extends forward to the sphenoidal region
(Fig. 266). At first the parachordal cartilages are separated from
one another posteriorly by dense tissue (Fig. 266) and the median
plate is similarly separated from the sphenoidal cartilage. Before
the end of the second month, however, the posterior extremities
of the parachordal cartilages become united ventral to the chorda
and the median occipital plate becomes fused to the sphenoidal
cartilage, at first laterally and then in the sagittal plane. The
chorda dorsalis at this period runs in dense tissue in a dorsal
groove in the occipital cartilage, then through this cartilage into
the retropharyngeal tissue, thence dorsalwards in the line of
suture between the occipital plate and the sphenoidal cartilage
and terminates dorsal to the sphenoid cartilage (Fig. 266).

Laterally a cartilaginous process extends out in the blastema
on each side of the hypoglossal nerve. The process caudal to

MORPHOGENESIS OF THE SKELETAL SYSTEM. 407

this nerve, as above mentioned, apparently, at times at least, has
a separate centre of chondrification, like the neural process of a
spinal vertebra, but this becomes much more quickly fused with
the body than does the latter. The apical lateral cartilaginous
process is formed considerably later than the caudal.

The hypoglossal foramen is at first completed by blastemal
tissue. In this tissue ventrolateral to the foramen there appears
a separate centre of chondrification. The cartilage arising here
soon becomes fused to the processes extending out from the
median plate on each side of the hypoglossal nerve, thus com-
pleting the cartilaginous boundary of the foramen and the pars
lateralis of the occipital cartilage. From it there extends in an
apico-Tfentral direction, lateral to the jugular foramen, a promi-
nent jugular process. The condyloid process is developed on the
caudal side of the posterior lateral process of the occipital (Fig.
264, p. 344).

Chorda Dor salts. — The suboccipital portion of the chorda
dorsalis becomes more and more irregular in form during the
third month. Small processes are given off, some of which become
separated from the chorda. In this region the chorda remains
longest united to the pharyngeal epithelium. Some processes of
the chorda are found, even in the second month, connected with
processes of the pharyngeal epithelium. The connections are
probably partly primary and partly secondary (Fig. 266). In
the fourth month the chorda usually becomes discontinuous in
places. After this it is gradually absorbed. During the chon-
drification of the basioccipital the chorda tissue is pressed back
between the dorsal side of the occipital plate and the tip of the
dens epistrophei. Chordomata may arise here.

The Labyrinth. — ^While the semicircular canals are being
differentiated the mass of tissue in which they are embedded
becomes somewhat loose in texture and gradually from without
medialwards becomes transformed into a peculiar kind of pre-
cartilage, the cells of which long remain nearer to one another
than in most cartilage (Fig. 31D). The cochlear portion of the
capsule becomes chondrified much later than the capsule of the
canalicular part. The semicircular canals are lined by epithe-
lium which abuts directly against the surrounding cartilage. The
fibrous coat of the labyrinth is gradually differentiated from the
cartilage. The oval and round foramens become distinct during
the period of chondrification, because the tissue which covers
them remains membranous while the surrounding tissue is con-
verted into cartilage.

The capsule of the labyrinth is at first incomplete (Fig. 310).
At the end of the second month the geniculate ganglion and the

408 HUMAN EMBRYOLOGY.

facial nerve lie in a slight groove on the vestibular portion of the
capsule (Fig. 310), while the cochlear and vestibular ganglia
extend into the large dorsal fissure between the canalicular and
cochlear portions of the capsule. As development proceeds the
anterolateral extremity of the dorsal edge of the cochlear portion

Fio. 310.— Modd

of th« right li^f of the ikuU of an embryo 2C mm. Iodb. 11» model is viewed from

above and thsmecliJH

it. The«.ur«.<.f«Qmeot therervesanindiraled. I, a«i«aj.tariDr; 2, heBuardi

of the firat cervid verl-

bra; 3, hemiarch o! the eeeond cen-insl vertebra; 4. liemiareh of the firat tboracic

7. canalis cmniopliaryn

arM; S.apguls nssslii

10. c«rtila«o Meekeli ; 11, diorda tjrapani; l2,eclodenn; 13, epiglottis; 14, incun;

15, lingua; 10, netvu*

ophthttlmi™* ; 19, nuT

■us petrosus superfic. major, near the geniruJate ganglion ; 20, course n( optic nen'e

througli optic fonuneii

nen'us abducent ; 24,

couree of the facial nerve between incus and auditory capfmle ; 25, course of the

26, course of vagus anil spinal accessory nen'»; 27, course of the hypoKlcwial

oerve; :;8, (Esophagus

29, aaceusendolymphBticuB: 30. septum nasi; 31, tectum poslerius; 32, tracbea.

of the capsule extends in a dorsolateral direction so as to cover
the two auditory ganglia. At the same time the groove containing
the geniculate ganglion and the neighboring portion of the facial
nerve becomes converted into a canal (Fig. 313). The saccus
endolymphaticus is not included in the otic capsule (Fig. 310).
Lateral from the foramen endolymphaticum, in which the ductus
endoljTiiphaticus is enclosed, lies the fossa subarcuata (Pig. 313).

MORPHOGENESIS OF THE SKELETAL SYSTEM. 409

In the human ehondroeranium it is not deep. In the petrosa of
children of from 2 to 10 years of age it is much deeper ; in adults
it again becomes slialLow (Mead).

Fio. 311.— L.to«] view of s modd of tha -k

ull of an embryo 20 mm. long. The eounw! of eomeof the

■wrvw Bre indies ted. Ala orbilalit. aSa. oibi^iia-.

Xfafemp., alBtemporali!i: ArcuiV. S. arch of firat tho-

nicic vertebra; B/.or*., biMtemaorbilale; Bl.mai

.. blastema iBBxillare; Cop..a.«(a.. aip»ul»»udiliv».p«n

conalic.i Cnp». muni,, rapsula naBslis: Cart, tr

<^.. esrtilB«o cricoidea; Can. Mm*., cutilago Meckel!.

lehind by (he lingual nerve; Cart, rttrr.. cart>lB<o thyT»-

oidm; Ch. Ivmp.. ehortiK tyiripani; C. 1-7. wmM

Bl the tip of the tmoubrlum n part of Ihs dense tissue which enraseo the whole raaaubriuni is shown;

medikl (□ this the CBVum tubotyinp»na]e may b

oeen; Mtal. ae. eit.. n>»t<» Bcuslicua extemru; N. aiv.

inf.. nen-ui alveol«i« interior; _V. ^u™^„ nerv

Lii> buceinaloriui; N. mandib.. nervus mandibularts; N.

moi.. uervuB maiiUariB. under cover of the ala

the opiic oen-e; jV. ///, counw of the oculomotor nerve;

N. IV. eour» of the troehl«r nerve; .V. VI. co

rse of the abduceni nen-e; N. VII, courae of the facial

nerve; JV. IX. muree of the glossopharynneal n

rve: N. X. eour« of the vagus nerve; N. XII. eourao

0.. Al«Hd.. o« hyoideum; beneath thi* the clavicle;

From the capsule of the labyrinth above the ossicles a process
grows forward (P. perioticus superior Gradenigo) {Figs. 311, 312,
313). Ventrally this extends into a piate composed of fibrous
connective tissue. This plate is connected with the pars cochlearis.

410 HUMAN EMBRYOLOGY.

The tegmen tympani is formed from the cartilaginous process and
the accompanying fibrous plate. The cartilaginous process is
well shown in Fig. 313.

Into the finer details of the development of the skeleton of
the internal ear we cannot here enter.

The cochlear portion of the capsule of the labyrinth is long
connected by a fairly dense mesenchyme with the median plate of
the occipital. After the chondrification of this portion of the
capsule it becomes fused to the cartilage of the median plate, form-
ing with it a continuous cartilaginous structure (Fig. 313). Across
the jugular foramen somewhat irregular bars of cartilage may
be formed (Fig. 313, right side).

In vertebrates below birds and nuumnals the auditory capsules lie in the lateral
wall rather than in the floor of the cranial cavity. In man the basal position of
the auditory capsules is more marked than in any of the lower mammals.

Tectum Postering. — The cranial vault, as previously pointed
out, is formed at first by a thin dense layer of membranous tissue,
which is closely applied to the lateral side of the capsule of the
labyrinth and extends ventrally into the dense tissue of the bran-
chial region. Posteriorlj^ and inferiorly it is attached to the pars
lateralis of the occipital. This membrane at first completes the
f. jugulare. In the sixth week cartilage begins to extend into it
from the posterior lateral (neural) process of the occipital. This
cartilage extends as a flat band rapidly in an anterior direction in
the membranous vault. In a 14 mm. embryo it has extended
anteriorly above the otic region, but lies at some distance from the
dorsolateral margin of the otic capsule. Soon after this it extends
in a ventral direction so as to be closely applied to the otic capsule
posteriorly and dorsally (Fig. 311), but even toward the end of
the second month it is still distinctly separated from this by a
narrow band of membranous tissue. Later the two become fused
(Fig. 313). Between the capsule and the margin of the cartila-
ginous vault there are several apertures for the passage of blood-
vessels.

During the third month the vault cartilages of each side
extend dorsally and become united so as to complete a flat bridge
of cartilage between the right and left occipitotemporal regions.
This bridge of cartilage is called the tectum posterius or synoticum.

The description here given of the development of the tectum posterius differs
in several respects from those of Levi, Bolk, and some other investigators. It is
based on a study of several embryos between 11 and 20 mm. in length which the
writer has had at his disposal. Possibly there are individual variations in the
mode of the development of the tectum.

Levi describes a squama occipitalis which arises from a separate centre of
chondrification, fuses with the pars lateralis of the occipital, and extends in an
anterodorsal direction in the membranous vault; and a squama temporalis, which

MORPHOGENESIS OF THE SKELETAL SYSTEM. 411

arises from a separate centre, fuses with the auditory capsule, and extends dorsally
into the membranous vault (Fig. 309). The squama occipitalis and squama tem-
poralis become fused and the temporal squama greatly reduced at the expense of
the occipital squama. The occipital squamsB fuse to form the tectum posterius.
According to Bolk, there is first formed a cartilaginous band, anterior interotic
band, between the auditory capsules or the parietal plates applied to these. The
posterior margin of this band extends into the membrana spinoso-occipitalis, which
is attached laterally to the ear capsules and to the partes laterales of the occipital
and posteriorly extends into the membrana reuniens dorsalis. Posterior to the
interotic band of cartilage a second band is formed by outgrowth of cartilage
from the partes laterales of the occipital and the caudal part of the otic capsule.
This latter cartilaginous band is separated from the former by a membranous in-
terval in which temporarily a pair of cartilages appear. There also appears in
front of the anterior interotic band a temporary centre of chondrification. In
the lower mammals there has frequently been described a cartilaginous lamina
parietalis lying above the auditory capsule and united to the commissura orbito-
parietalis.

ORBITOTEMPORAL REGION.

In man the cartilage of the orbitotemporal region, forms the
basis for the ossification of the body, of the orbital and tem-
poral wings, and of the laminae laterales of the processus ptery-
goidei of the sphenoid. These parts have special centres of chon-
drification which at first are separate but which fuse later.

The chondrification of the body of the sphenoid begins in the
median line anterior and ventral to the apical end of the chorda
dorsalis in embryos between 12 and 13 mm. long. The position of
this cartilage in a 14 mm. embryo is shown in Fig. 266. Prom
this centre an arm of cartilage (Rathke's Schadelbalken) extends
forward on each side of the hypophyseal pocket. In front of this
the two processes unite to form the anterior part of the body of
the sphenoid.

In the lower vertebrates a pair of cartilages, trabeculae, are formed, one on
each side of the hypophysis. These cartilages usually unite with one another
apically and with the occipital parachordal cartilages caudally. It is a question
whether or not these trabecul© are homologous with the sphenoidal cartilage above
described (see Gaupp, 1906, p. 826).

The caudal part of the body of the sphenoid becomes fused
with the apical end of the median occipital plate and sends a
process, the dorsum sellae, upward toward the midbrain fold. The
apical end of the chorda comes to lie in the cartilage at the base
of the dorsum sellae or between the cartilage and the perichondrium
of the sella turcica or of the dorsum sellae. In the cartilage the
chorda soon disappears; under the perichondrium it persists
longer than elsewhere in the cranium and may give rise to chordo-
mata (Williams). The cartilaginous body of the sphenoid grad-
ually assumes the shape characteristic of the adult bone. During
the third month the fossa hypophyseos, the tuberculum sellae, and
the sulcus chiasmatis become fairly distinct (Fig. 313).

412 HUMAN EMBRYOLOGY.

The hypophyseal canal is at first relatively large and is much
broader than it is long. The tissue immediately about is very
slowly converted into cartilage during the third month. Occa-
sionally a patent canal is found in the adult bone.

The cartilaginous ala temporalis (see Fig. 310) arises in the
orbitotemporal blastema some distance below the membrane which
forms the floor of the cranial cavity. It is only at a much later
period that the temporal wing helps to bound the cranial cavity.
During the latter half of the second month two portions may be
distinguished in the ala temporalis, a medial and a lateral (Figs.
309 and 310).

The medial portion (processus alar is, Hannover) lies in the
plane of the body of the sphenoid. It consists at first of blastemal
tissue which extends from the body of the sphenoid opposite the
hypophysis laterally and then posteriorly so as partially to enclose
the internal carotid artery. It has a special centre of chondrifica-
tion. It approaches closely but does not fuse with the otic capsule
(30 mm. fetus). A closed foramen caroticum is found in several
mammals, but is transitory when present, and probably is not
constant in the human embryo (Levi).

The lateral part of the ala temporalis arises in a plane ventral
to the medial part. The condensed blastema of which it is at
first formed becomes fused to the ventral surface of the medial t

part near where this turns posteriorly about the internal carotid
artery. The lateral part of the ala temporalis is small where it
joins the medial part, but expands rapidly as it extends laterally,
anterior to the otic capsule and ventral to the cranial border of
the trigeminus ganglion. It has a separate centre of chondrifica-
tion. The lateral part becomes cartilaginous later than the medial
but becomes ossified much sooner (Fig. 313). From the ventral
surface of the medial end of the lateral portion of the ala tem-
poralis a short process extends ventralwards. This represents the
anlage of the lateral lamella of the pterygoid process.

The ganglion of the trigeminus lies at first caudal to the
lateral part of the ala temporalis, and the first and second branches
of this nerve as well as the motor nerves of the eye pass forward
medial to this process. During the period of chondrification the
second branch of the trigeminus becomes enclosed in the foramen
rotundum. The third division of the trigeminus at first passes
down between the ala temporalis and the otic capsule. It later
becomes embedded in a groove on the posterior margin of the
ala temporalis. This groove is converted into the foramen ovale
before or during the period of ossification. The foramen spinosum
is similarly formed about the middle meningeal artery.

The ala orbitalis is differentiated from the orbitotemporal
blastema first by condensation of tissue and then by chondrifica-

MORPHOGENESIS OF THE SKELETAL SYSTEM. 413

tion. It is larger at first than the ala temporalis. In a 14 mm.
embryo a blastemai process, the taenia metoptica of Gaupp, arises
from the side of the body of the sphenoid, extends up behind the
optic nerve and then over this into a plate of membranous tissue
which forms the roof of the orbit and the floor of the cranial cavity.
A second blastemai process, taenia preoptica, extendts from the
side of the anterior extremity of the body of the sphenoid in front
of the optic nerve laterally into the orbital plate. Chondrification
(Fig. 310) appears first in the taenia metoptica in the region pos-
terior to the optic nerve, and from here extends medialwards to
fuse with the anterior part of the body of the sphenoid and lateral-
wards into the orbital plate (Fig. 313). The orbital plate has a
separate centre of chondrification. The taenia preoptica appar-
ently becomes chondrified through extension of cartilage into it
from the body of the sphenoid. Chondrification begins later in
this than in the taenia metoptica and the orbital plate. During
the third month the ala orbitalis becomes fused into a single piece
of cartilage and at the same time joined by bands of cartilage
(cartilago spheno-ethmoidalis) to the lateral edge of the cribri-
form plate of the ethmoid (Fig. 313).

In many mammals the outer end of the ala orbitalis is connected with the
cartilage of the cranial vault dorsal to the otic capsule (parietal plate) by a bridge
of cartilage, the commissura orbitoparietalis (Gaupp). This bridge, which is
lacking in man, encloses a large (sphenoparietal) foramen.

ETHMOroAL REGION AND THE NASAL CAPSULE.

The ethmoidal region and the nasal capsule are the last por-
tions of the chondrocranium to become cartilaginous. In an
embryo 20 mm. long and in the eighth week of development (Figs.
310 and 311) the tissue is still membranous, although both the
nasal septum and the lateral wall of the nasal capsule are evi-
dently in a precartilaginous stage. In the third month the car-
tilaginous capsule is extensively developed (Figs. 312 and 313).

The chondrification of the septum apparently takes place by
anterior extension from the cartilage of the ventral part of the
body of the sphenoid. The septum is at first relatively thick,
especially on the ventral margin. From the anterior part of this
thickened ventral margin of the septum a **paraseptal" cartilage
becomes isolated on each side (third month).

In many of the lower mammals the anterior part of the ventral margin of
the septum becomes joined to the lateral wall by a band of cartilage, the lamina
transversalis anterior, thus separating the " fossa narina " from the " fenestra
basilaris." The paraseptal cartilage in these mammals extends from the posterior
margin of the lamina transversalis anterior into the fenestra basilaris. In man the
lamina is not developed, so that a long fissura rostroventralis is present in the

414

HUMAN EMBRYOLOGY.

nBsal capsule. The paraseptal cartilage primitively in mammals, but not in the

repliles, furms a sheath for Jacobson's organ, but in mao it has lost this function.
It, however, persists until after birlb (E. Schmidt).

According to Mihalkovics, several isolated pieces of cartilage found in the
third month lateral to the inferior margin of tbe nasal septum may indicate rudi-
ments of the L, transversalis anterior.

CsnilBga Meckali

Posteriorlj' the cartilage of the nasal septum is much nar-
rower than it is anteriorly. It does not extend into the blastemal
septum between the nasopharyngeal passages.

The chondrtfication of the lateral walls (C. paranasalis) of
the Dasal fossa; seems to take place independently, but the lateral
cartilage is soon joined to the nasal septum, anteriorly forming
the cartilaginous roof and sides of the nose, tectum nasi, and
paries nasi, and somewhat later it is posteriorly united to the
region where the sphenoidal cartilage passes over into the carti-
lage of the septum. Through infolding of its inferior margin the
lateral wall of the nasal fossa posterior to the narina nasi furnishes
the anlage of the maxillary turbinate, concha inferior. This is at

MORPHOGENESIS OF THE SKELETAL SYSTEM. 415

first simple in form though later more complicated. Late in the
third month it develops an accessory process curved upwards,
and in the fifth month exhibits extensive folds (Mihalkovics). It
becomes separated from the lateral wall when the latter undergoes
retrograde metamorphosis (seventh month, Killian).

During the blastemal period folds in the surrounding mesen-
chyme project into the nasal fossa. On the posterior dorsal part
of the lateral wall there is formed a fold of tissue which, according
to Peter (1902), may be looked upon as having been derived from
the caudodorsal part of the median wall. This fold gives rise to
the anlage of the middle turbinate, concha media. The anlage of
the superior turbinate arises in a manner similar to the middle.
Following this there are formed much later the anlages of three
more turbinate processes. Thus there are five chief ethmoido-
turbinate processes in addition to the maxilloturbinate already
described. Apiealwards, between the concha media and the concha
inferior, there appears a rudimentary nasoturbinate which gives

416 HUMAN EMBRYOLOGY.

rise to the agger nasi and the uncinate process. (See Killian,
1895, 1896; Peter, 1902.)

Besides the chief turbinates there are numerous accessory
turbinates. The bulla ethmoidalis arises from accessory processes
in the meatus beneath the middle turbinate. The complicated
changes which take place in the nasal turbinates cannot be entered
upon in detail in this section.^

Chondrification of the ethmoidal turbinates, of the uncinate
process, and of the bulla ethmoidalis begins in the fourth month.

The cartilaginous capsule of the nose at first is open toward
the olfactory bulb, but during the third month the cribriform plate
is formed by chondrification of tissue between various nerve
bundles (Fig. 313). The lamina cribrosa is characteristic of mam-
mals, but is not present in all.

In most of the lower mammals the caudal margin and the
caudal part of the inferior margin of the lateral wall of the nasal
capsule bend towards the nasal septum and then forwards so as to
bound a cupola-shaped recess (the sinus terminalis) at the caudo-
dorsal extremity of the nasal fossa. In man this recess, the anlage
of the sinus sphenoidalis of the osseous cranium, is not much
developed and has no ventral cartilaginous wall. A membranous
septum is, however, formed between the meatus nasopharyngeus
and the cupola-shaped recess. The septum becomes ossified, form-
ing the floor of the sphenoidal sinus. The paranasal cartilage
bounds the recess laterally, but does not bound the meatus naso-
pharyngeus. The latter becomes bounded laterally by a membrane
bone (os pterygoideum).

In the third to fourth month a short cartilaginous process
(proc. paranasalis) arises from the lateral wall of the nasal cap-
sule and encircles the lachrymal duct.

The fate of the cartilaginous nasal capsule is varied. Parts
become ossified, parts are converted into connective tissue or dis-
appear, and parts pass over into the cartilaginous portion of the
skeleton of the adult nose. The greater part of the posterior por-
tion of the capsule becomes ossified as the ethmoid bone. The
dome-shaped wall of the sinus terminalis gives the basis for the
concha sphenoidale (ossiculum Bertini). The maxilloturbinate
(concha inferior) and a part of the nasal septum likewise become
ossified. Parts of the septum and of the inferior portion of the
lateral wall above the maxilloturbinate, however, disappear and
are replaced by parts of the neighboring membrane bones. The
cart, paraseptalis remains till after birth. A large part of the
septum and parts of the roof of the nose remain cartilaginous
throughout life. The C. alares majores become separated by

* See the description of the development of the nose in the section on the
organs of special sense.

MORPHOGENESIS OP THE SKELETAL SYSTEM. 417

development of connective tissue from the rest of the nasal cap-
sule during the fourth to fifth month of intra-uterine life. The
C. alares minores and the C. sesamoidia; are differentiated from
the C. atares majores. The cartilago spheno-ethmoidalis, the
orbital wing of the cartilaginous ethmoid, which during the third
month extends as a broad plate between the lateral margin of the
lamina crlbrosa of the ethmoid and the ala orbitalis of the sphenoid
(Fig. 313), in the fourth to fifth month is broken up into several
pieces and absorbed.

u, 1907. Fi(. 366.J VisMnl skeleton of th»
tuB 8 cm. lon(.

DEEIVATIVES OF THE VISCERAL ABCHES.

From the visceral arches are derived the bones of the middle
ear, the styloid process of the temporal bone, the stylohyoid liga-
ment, the hyoid bone, and the cartilago thyroidea. In the human
embryo the formation of the blastemal ossicles and of the hyoid
bone is a fairly direct process, but their relations to the embrj'onic
skeleton of the mandibular and hyoid arches (Meckel's and
Eeichert's cartilages) are more or less clearly marked. The rela-
tions of the laryngeal cartilages to the visceral arches are not so
definite.

418 HUMAN EMBRYOLOGY.

Toward Uie end of the first month the tissne in the branchial
arches, in the lateral region of the head immediately dorsal to
these, and about the larynx becomes much condensed. According
to I. Broman, the tissue in the dorsal part of the mandibular arch
region is divided by the third division of the fifth nerve into lateral
and medial portions, while that in the hyoid arch region is simi-
larly divided by the seventh nerve. The relations of these divi-
sions of the blastema of the first two arch regions to the auditory
ossicles are described as follows:

The proximal portion of the lateral part of the blastema of
the mandibular arch region gives rise to the anlage of the incus.
From this in a 14 mm. embryo a process of condensed tissue may

Fia. 315.— (After Bronuo. AnmtomiKhc Hefte. 1897. vol.

u. T»(. C. Fi««. 6. 7. and 9.) Three 6«.i

to llliutnts the developmeot of the bonvi of U>« middls ear.

The models lire vieCBit (nun the mei

-ide. FiB. A. From bd embryo 18 nun. long; aagn. 1 : 30.

Fig. B. From u. mbryo 20.6 mm. lo

nia«i>. I : 30. F«. C. From > [etiu S5 mm. long; atgn. 1 :

5. ^nn. I., lonuliu tympejuciu: Ch

chorda tympuii; Cap., capitulum mgjleir Cop*, aud.. «psul

audibva. pars caDaliciilsrii; Cr, I., e

longum ineudui; Hb. «.. hyoid i«h, mecliil portion; Ih.. inte

P.. pro<»»ua loDvu (folii) mallei; Pr

proeeuiu l>(«r>lis m^lei: R. «n., Heichert's c»rtiU«e; S. m.

euleui malleolarii; St.. stapes; K N.

■emiDus: VII, N. VII [uialii.

be followed anteriorly, lateral to the fifth nerve, into the anlage
of the maxilla. This later disappears. The anlage of the incus
soon fuses with the blastema of the otic capsule {Fig. 315, A),
but becomes separated again at the time of chondrification. The
proximal part of the lateral division of the blastema of the hyoid
arch region gives rise to the anlage of the tympanohyale (latero-
hyale). This in turn becomes fused to the capsula auditiva and to
the styloid process (Fig. 311).

The cartilage of the external ear is differentiated from the
blastema of the dorsolateral region of both the mandibular and
the hyoid arches.

The proximal end of the medial part of the blastema of the
mandibular arch region is checked in development by the vena
jugularis primitiva. The portion beyond this gives rise to the
anlage of the malleus (Fig. 311), and this is continued into a

MORPHOGENESIS OP THE SKELETAL SYSTEM. 419

condensed band of tissue that may be followed in the mandibular
arch to the mid-ventral line. This band is the anlage of Meckel's
cartilage and appears in an embryo 11 mm. long as a rod of dense
tissue.

The proximal end of the medial part of the blastema of the
hyoid arch region gives rise to the anlage of the stapes (Fig.
311). 21 This anlage is from the first connected by a band of
blastemal tissue with the anlage of the incus. The band of tissue
develops into the crus longum incudis (Fig. 315, C).^^

Immediately ventral to the anlage of the stapes there is
formed a small band of tissue (interhyale, Broman; lig. hyostape-
diale, Fuchs), which connects this anlage with the main hyoid
arch. It lies beneath the facial nerve (Fig. 315, A and B). It
forms a partial sheath for this nerve. In the second month it
disappears, so that the stapes anlage is no longer connected with
the main hyoid scleroblastema. The latter is a rod-like process
which extends from the tympanohyale (laterohyale) medialwards
to the anlage of the body of the hyoid bone. It is visible in an
11 mm. embryo.^^ It gives rise to the styloid process, the stylo-
hyoid ligament, and the lesser comu of the hyoid bone.

It is convenient to consider the development of the ossicles
and of Meckel's cartilage separately from the development of
the hyoid bone, the styloid process, and the laryngeal cartilages.

THE OSSICLES AND MECKEL 's CARTILAGE.

During the latter half of the second month Meckel's cartilage
becomes chondrified. Its position at this period is shown in Fig.
311. It does not reach quite to the mid- ventral line. Later it
sends a process upwards parallel to the medial line (see Figs.
312-324).

Dorsally Meckel's cartilage is continued into the capitulum
of the malleus (Figs. 311, 314, 315, B and C).^*

Toward the end of the second month the malleus is fairly well
diflferentiated (Figs. 311 and 315, B). The manubrium extends
medialwards in a dense mass of tissue which intervenes between

'"According to Hugo Fuchs (1905), in the rabbit the anlage of the stapes
lies dorsal and anterior to the hyoid arch region and arises not in connection with
the hyoid arch but rather in connection with the otic capsule. There is later formed
a temporary connection between the anlage of the stapes and that of the skeleton
of the hyoid arch, the " ligamentum hyo-stapediale."

""According to Fuchs (1905), in the rabbit the anlage of the erus longum
of the incus arises apparently independently of the main anlage of the incus.

"According to Fuchs (1905), in the rabbit it first appears in the region of
the hyoid bone and thence extends dorsalward.

**Acx?ording to Fuchs (1905), there is a common malleus-incus anlage in the
rabbit, which arises independently, chondrifies from a separate centre, and becomes
secondarily fused to Meckel's cartilage. The latter arises, according to Fuchs, from
a centre which lies in the region where the temporo-mandibular joint is later dif-

420 HUMAN EMBRYOLOGY.

the lateral extremity of the tubotympanic cavity and the medial
end of the external auditory meatus.^^

In Fig. 311 the most medial part of this tissue and the medial
extremity of the external auditory meatus are shown. From
the manubrium a ** lateral" process is at first directed downwards.
As development proceeds the manubrium comes to be directed
downwards and the lateral process is turned outwards. The crista
mallei arises during the fourth month. It is not due to the out-
growth of a process, but rather to absorption of the underlying
cartilage. The joint surfaces between the malleus and incus have
from the first two chief facets, as in the adult. The greater facet
is at first directed laterally, the smaller dorsally. When rotation
takes place the greater facet faces dorsally, the smaller medially.
At the beginning of the third month the accessory facets of the
joint surface and the **Sperrzahn" of Helmholtz appear. The
cartilaginous malleus is at first joined to the cartilaginous incus
by dense tissue, in which later a joint cavity arises.

The incus (Figs. 311, 314, and 315, B and C) becomes chondri-
fied during the latter half of the second month. It has a special
centre of chondrification, which first appears in the head and then
extends to the processes. The head at this period is embedded in
dense membranous tissue (Fig. 310).

Cartilage extends into the cms longum as far as the joint
between it and the stapes. This joint is at first composed of
dense tissue but is later diflferentiated into a true joint. The cms
brevis is formed when chondrification starts in the anlage of the
incus. At this p)eriod the head of the incus becomes somewhat
separated from the capsule of the labyrinth, with which it has
been temporarily fused. A short blastemal process is left which
extends dorsally from the incus to the capsule. Into this process
the cartilaginous cms breve extends. In Fig. 311 the space
between the cms breve and the auditory capsule is shown slightly
too wide in order to reveal the deeper structures. The processus
lenticularis is not formed until the crus longum has begun to ossify.
At the beginning of the third month the crus breve, cms longum,
and the manubrium of the malleus lie nearly in a plane, a con-
dition noted by Helmholtz in the adult. The malleus and Meckel's
cartilage are homologous with the skeleton of the lower jaw in

ferentiated, and from which the articular part of the squamosum also arises.
According to Fuchs, the mandibular joint of mammals is homologous with the
quadrato-articular joint of the lower forms. According to most investigators, the
quadra to-articular joint is homologous with the malleus-incus joint in mammals,
a view originally advanced by Reichert. See Gaupp (1906), Van Kampen (1905),
Mead (1909).

"According to Fuchs (1905), in the rabbit the manubrium arises separately
from the anlage of the head of the malleus, to which it extends from the hyoid
arch region.

MORPHOGENESIS OP THE SKELETAL SYSTEM. 421

the inferior vertebrates. The incus is homologous with the quad-
rate portion of the palato-quadrate. The palate portion is not
represented.^

The first definite diflferentiation of the stapes is seen when
the cells of the anlage form a ring of tissue concentrically arranged
about the stapedius artery. This is at first separated from the
capsule of the labyrinth by loose tissue, but later becomes fused
to it, although still distinguishable by the arrangement of the
cells. When chondrification sets in, it becomes still more clearly
marked oflF. From the first it has an oblique position (about 45^
to the horizon). Chondrification begins during the latter part of
the second month. At the end of the third month the hitherto cir-
cular stapes begins to take its definite form. The artery persists
to the end of the third month. As the foot-plate of liie stapes
becomes differentiated the lamina fenestris ovalis becomes thin.

•

TYMPANOHYALE, BEICHERT's CARTILAGE, THE HYOID BONE, AND THE

LARYNGEAL CARTILAGES.

The tympanohyale (laterohyale) arises from the proximal
part of the lateral blastema of the hyoid arch region. It becomes
chondrified from a separate centre and then proximally fuses to
the cartilaginous otic capsule, while distally it becomes fused with
the chief cartilage of the hyoid arch. The part of the otic capsule
with which the tympanohyale fuses is a process that lies on the
ventrolateral ^nrface of the promontory of the lateral semicircular
canal, the crista parotica. The processus perioticus superior is
developed at the apical end of this crest. The proximal end of
the tympanohyale is enclosed in the tympanic cavity and utilized
in the formation of the wall of a canal containing the nervus
facialis, the musculus stapedius, and a few blood-vessels (foramen
stylomastoideum primitivum, Broman).

The chief blastemal skeletal element of the hyoid arch is a
rod of tissue which is proximally connected both with the anlage
of the stapes and with that of the tympanohyale. Distally it
extends to the lateral margin of the anlage of the body of the
hyoid bone. It loses its proximal connection with the stapes,
becomes chondrified from a separate centre and finally fused with
the distal end of the cartilaginous tympanohyale (Figs. 311, 314).
It is now known as Reichert's cartilage. Subsequently it becomes
transformed into the lesser cornu of the hyoid, the stylohyoid
ligament, and the styloid process.

It has been pointed out above that the mesenchyme of the
visceral arches toward the end of the first month becomes verv
dense and that a dense mass of tissue surrounds the anlage of

See, howe\'er, note 24, p. 419, and note 43, p. 141.

422 HUMAN EMBRYOLOGY.

the larynx. This mass of tissue is especially developed ventral
and lateral to the larynx and is connected with the dense blastema
of the hyoid and of the more posterior visceral arches. During
the second month tliere are developed in this tissue the anlages of
the body and of the greater cornua of the hyoid bone and of the
laminsB and the cornua of the thyroid cartilage of the larynx.

The appearance of the structures mentioned above toward
the end of the second month is shown in Fig. 311. Their appear-
ance about the middle of the second month is shown in Fig. 316.

The body of the hyoid is developed from the ventral part of
this dense tissue in front of the proximal end of the larynx. It
may be barely distinguished in an 11 mm. embryo. Pl-ecartilage
appears in it in a 14 mm. embryo. At about this time it has the
form shown in Fig. 316, A and B. The form is essentially similar

c

Fia. 316.— (After Kallius, Anatomische Hefte. 1897, vol. ix, Taf. XXVI, Figs. 20, 21, and 22.)
Three figures to illustrate the development of the hyoid bone and the laryngeal cartilages. A and B.
hyoid, hyothyreoid, and thyroid cartilages, from an embr3ro 39-40 days old: A, ventral view; B. lateral
view. C. Medial view of the cricoid cartilage of an embryo 40-42 days old. The ceotra of chondri-
fication are outlined by heavy lines. C. m., comu minus; C. hyothyr., cartilago byothyreoidea; Thyr^
cartilago thyreoidea.

at the end of the second month (Fig. 311), but it is still composed
largely of dense tissue and precartilage. During the third month
it becomes more highly differentiated. The body of the hyoid
bone probably represents a copula of a visceral arch or the fusion
of two such copulaB. Kalliiis found in the cow an anterior and a
posterior anlage, the former of which may represent a hyoid, the
latter a third visceral arch copula. No such double anlage has
been found in man.

The anlage of Reichert 's cartilage in the 11 mm. embryo above
mentioned is more highly developed than the body of the hyoid.
It is composed of a very dense tissue, which is connected with
the blastema of the body. When chondrification takes place
Reichert 's cartilage long remains separated from the cartilage of
the body of the hyoid by a narrow band of dense tissue which
forms a kind of primitive joint. Finally the two cartilages become
fused.

Between the body of the hyoid bone and the laminae of the
thyroid cartilage in the dense tissue lateral to the larynx there is

MORPHOGENESIS OP THE SKELETAL SYSTEM. 423

developed a curved cartilaginous bar, which we may call the hyo-
thyroid cartilage (Figs. 311, 316, A and B). Ventrally this bar
is joined at first by dense tissue, later by cartilage, to the back of
the body of the hyoid. Dorsally it becomes fused to the cartilage
of the lamina of the thyroid. It is invisible in an embryo of
11 mm. and becomes chondrified apparently from a single centre
at about the time of the chondrification of Reichert's cartilage.
It represents the skeleton of the third and a part of the fourth
visceral arches. Its ventral portion becomes the greater cornu
of the hyoid bone and its dorsal inferior portion the superior
cornu of the thyroid cartilage. The two portions become dis-
continuous at the end of the third month, so that a small cartilago
triticea is separated on the one side from the great cornu of the
hyoid bone and on the other from the superior cornu of the
thyroid cartilage. Connective tissue serves at the same time to
form connecting ligaments, but the definite lig. hyothyroideum
is not well developed until after birth, when the hyoid bone becomes
further separated from the thyroid cartilage.

The blastemal laminae of the thyroid cartilage appear about
the middle of the second month. One appears on each side at the
p)eriphery of the dense tissue surrounding the ventral part of the
larynx. This anlage has the form of a slightly curved quadri-
lateral plate in which a foramen may be seen (Fig. 316, B). There
are two centres of chondrification, one cranial and the other caudal
to the foramen. The cranial centre is continuous with the hvo-
thjToid cartilage and later becomes united on each side of the
foramen to the cartilage of the caudal centre. The foramen is
usually closed by cartilage, but occasionally remains patent
throughout life. The inferior cornu is developed from the dorsal
part of the caudal margin of the lamina. Ventrally the laminae
of each side become united by the membranous tissue into which
the cartilages of the cranial and caudal margins of the laminae
extend, and finalljr unite in the mid-ventral line. Between the
two margins there is an orifice closed merely by membrane. In
this a special centre of chondrification appears. This medial car-
tilage eventually becomes united to the cartilage of the laminae,
so that the central orifice is closed in the tenth to thirteenth week
(according to Kallius). The cranial margin of the thyroid car-
tilage is at first nearly level. The incisura arises through the
rapid development of the laminae lateral to the median line. The
cornu inferius, the tuberculum superius and inferius, and the linea
obliqua are developed during the latter part of the fourth month.

The thyroid cartilage is supposed to be derived from the
fourth and fifth visceral arches. The central cartilage probably
represents copulae.

424 HUMAN EMBRYOLOGY.

The cricoid cartilage is the first of the cartilages of the larynx
to show definite hyaline tissue. About the lower part of the
larynx there is formed a dense band of tissue. In this tissue a
semicircular cartilaginous process appears. (In Fig. 316, C, the
cartilage is surrounded by dark lines.) It is bilaterally better
developed than in the mid-line, but if there are two bilaterally
placed centres these quickly fuse ventrally. The cartilage slowly
develops in the dorsal direction. Fig. 311 shows it at the end of
the second month. In the third month the ring is completed and
the posterior lamina is developed.

The arjiiSBnoid cartilage develops from the blastema continued
cranialward from the cricoid cartilage (Fig. 316, C). A special
centre of chondrification appears in the seventh week. The first
part of the cartilage developed represents the posterior portion,
chiefly the proc. muscularis. From this the processus vocalis
grows ventrally. This process, however, is long blastemal and
does not reach its definitive form till the end of the fourth month
(Kallius). The apex of the cartilage grows cranialwards, so that
the definitive form of the cartilage, with the exception of the
proc. vocalis, is approached by the end of the third month. There
is regularly present in later fetal life on the arytaenoid cartilage
ventral to the cart, comiculata a process which disappears after
birth. Its place is marked by the origin of the ligament which
extends to the cartilago cuneiformis. It is probable that it rep-
resents the cartilaginous process which connects the arytaenoid
and cuneiform cartilages in some animals (Kallius).

The blastemal anlage of the cart, corniculata is continuous
with that of the cart, arytaenoidea. Toward the end of the third
month it chondrifies from a special centre.

The cartilage of the epiglottis does not appear until the end
of the fifth month. It has a single median centre.

The cuneiform cartilages develop in the blastema of the
plicaB aryepiglotticsB. They appear toward the end of the seventh
or early in the eighth month.

Period of Ossification.

In the human skull the membrane bones are extensively devel-
oped, compared with those in lower forms. Some of the centres
of ossification in the membranous tissue arise before any of the
centres in cartilage. Thus Mall (1906) has found centres of ossi-
fication for the mandible (39th day), maxilla (39th day) and pre-
maxilla (42d day), before any centre of ossification has appeared
in the chondrocranium. The first centres of ossification to appear
in the chondrocranium are those in the occipitale laterale (56th
day), the basioccipital (65th day), orbitosphenoid (83d day), and
basisphenoid (83d day).

MORPHOGENESIS OP THE SKELETAL SYSTEM. 425

The complexity of tiie ossification of the bones of the skull
makes it advisable to discuss briefly the development of each of
the iudividnal bones recognized in the hnman skull rather than
to treat of the bones in classified groups. Most of the bones of
the human skull arise from two or more centres of ossification,
some of which represent individual bones in the lower vertebrates.

08 OCOIPITALE.

In the occipital bone five elementary parts may be distin-
guished, a basal (basioccipital), two condylar (oecipitalia lateralia,
exoccipitals), an occipitale superius (squama, inferior part), and
an interparietal (squama, superior part). The interparietal arises
in membranous tissue, the other parts in cartilage.

Fia. 317.— (After

Ssppey. Tr

uliS d'Anitomis, F^. 12.)

• OMdpital bone. A.

Embryo of two months

l,a««fi«t

on in the buitHjoipitai; 2,

occipital; 3, oceipitale

auperiiis ; *. carlil««o.

B. Fetui d

( three months : 1. bMioo

ripiUj ; 2. occijBtBle

JatenJe: 3, condyle;

4-. occipilAle niperiuB

4', intMiiB

6', cartilne; B', m

embranoua portion of

il^tBle Utenlc; 3.

Dondyle ; 4. aanculum

■I occipital

protuberance; 8. («^1»«0

The basioccipital and the two oecipitalia lateralia arise each
from a separate centre of ossification in the ehondrocranium, and
at birth are still separated from one another by cartilage (iPig.
317, A, B, C). The centres for the oecipitalia lateralia appear on
the 56th day and that for the basioccipital on the 65th (Mall).

The occipitale superius and the interparietal are at birth
fused into a single plate of bone.^'' The occipitale superius arises
from four, the interparietal from two centres of ossification (Mall).
According to Mall, the first centres of ossification to appear are
two bilaterally placed centres for the occipitale superius which
arise in the cartilage immediately dorsal to the foramen magnum
(55th-56th day). These two centres soon imite across the mid-

" By some authors the bone here called occipitale superius is designated infra-
occipital; and the bone here called interparietal is called supra-occipital. {See
Poirier, Traite d'Anatomie, vol. i, p. 408-109,)

426 HUMAN EMBRYOLOGY.

line,^® and are joined by two secondary centres, one of which
arises on each side. Occasionally an additional unpaired median
centre appears on the dorsal margin of the foramen magnum.^
More often, however, there arises a small process, on the inferior
margin of the squama in the medial line (Fig. 317, C, 4). This
process, later enclosed by bone, gives origin to the crista occipitalis
interna (Lengnick, 1898).

The two bilaterally placed interparietal centres appear on
the 57th day in the membranous tissue which extends anteriorly
from the occipitale superius. They are rectangular in form and
unite on the 58th day to form the interparietal bone. The inter-
parietal unites with the occipitale superius in the first half of the
third month of intra-uterine life to form the squama of the occipi-
tal. Fusion takes place in the median line before it does laterally ;
at birth the lateral fusion is usually incomplete. The interparietal
may remain partially or wholly separated from the occipitale
superius throughout life. In many of the lower manmials the
interparietal normally remains distinct from the supraoccipital.
According to Ranke, the squama occipitalis arises from four pairs
of centres of ossification. Various investigators diifer consid-
erably in the number of centres which they ascribe to this part of
the occipital. Anterior to the interparietals a pair of pre-inter-
parietal bones (Fig. 317, B) are apparently not infrequent. The
osseous union of the occipitale superius and the occipitalia lateralia
begins in the first or second year and is completed in the second
to fourth year; that of the basioccipital and the occipitalia latera-
lia begins in the third or fourth but is not completed until the
fifth or sixth year or later. The basioccipital forms the anterior
fourth or fifth of the condyles. Some authors describe condylar
epiphyses. The basioccipital is united to the basisphenoid by car-
tilage up to about the twentieth year (16th to 20th, Toldt). Ossific
union is completed one or two years later (Quain's Anatomy,
10th ed.). Epiphyseal discs like those which complete the bodies
of the vertebrae are described as arising and fusing with the con-
tiguous surfaces of the basisphenoid and basioccipital before the
two bones become united by synostosis. At the centre of the
synostosis a mass of fibrocartilage frequently long persists. Rem-
nants of the chorda dorsalis may likewise persist here and give
rise to tumors. (See Poirier, Virchow, Welcker, Luschka,
Steiner.)

" According to Toldt, instead of two there may be a single medially placed
centre. According to Bolk (1903), the ossification arises in the membranous part
of the tectum synoticum.

"* Ossiculum Kerckringii, Kerckring, 1670, Manubrium ossis occipitalis, R.
Virchow. Ranke showed that it arises in cartilage and membranous tissue. Bolk
found in one instance an independent cartilaginous nucleus in this region.

MORPHOGENESIS OF THE SKELETAL SYSTEM. 427

Considerable variation is found at the base of the occipital
bone. {See Swjetscbnikow, 1906, p. 155.) Variations of this
kind are associated with variations of the atlas.

OS SPHENOIDALE.

In man the sphenoid bone arises chiefly from ossification
centres which appear in the orbitotemporal region of the chondro-
cranium. To it several hones of membranous origin become fused.
In the sphenoid one may distinguish fourteen centres of ossifica-
tion: four in the basisphenoid, two presphenoid, two alisphenoid,
two orbitosphenoid, two pterygoid, and two intertemporal. In

•t Auitomy. lOUi ed^ vol. il. Pt. I. Tig. TS.> Ostification of sphenoid
ID early period, seen from above: I, the als temporalea oeeified; 2, the alie
ion hu rncireled Ibo optic Fommen. ukd a miall luture is diitiDguishable at
3, nuclei of basisphenoid. B. Back part of the boae shown in A: *. mediaJ
. C. ICopied from Heckd, Archiv. vol. i, lab. vi, Fig. 23i, and stated to be
4. Duclai ot piesphenoid; 5, separate lateral proceeaea of the body (UngulKl:

ined to th« baaiapbeaoid and the medial plerygoid plalca (not ecen in the

addition to these centres there are several in tlie ossicula Bertini
which in part fuse with the presphenoid after birth. (See below.)

In each of the greater icings, alisphenoids, a centre of ossifica^
tion appears toward the end of the second month in the chondro-
cranium between the maxillary and the mandibular nerves. From
this centre ossification extends into the lateral lamina of the ptery-
goid and into the lateral portion of the greater wing (Figs. 322
and 318, A and C). From the main centre a lamella of bone is
usually formed about the mandibular branch of the trigeminal
ner\'e, thus separating a foramen ovale from the foramen lacerum.
According to some authors, there are two centres of ossification in
the alisphenoid and external pterygoid which fuse together at an
early period (Sappey).

Tn the latter part of the third month (Mall) a bilaterally placed
pair of centres appears in the basisphenoid (Fig. 322 and Fig.

428 HUMAN EMBRYOLOGY.

318, A). The two centres unite in the fourth month. After this
union two other centres arise (sphenotics, Sutton, 1885), give
origin to the lingulae, and fuse with the body (Fig. 318, C). The
superior margin of the alisphenoid is strengthened by a mem-
branous bone (Hannover, 1880). This bone, called the os inter-
temporale by Ranke, occasionally persists as an independent struc-
ture or may be fused to the squama temporalis or to the frontalis.

The nuclei for the medial pterygoid plates appear in the
second month (57th day. Mall) (Fig. 318, B). They fuse with the
nuclei of the greater wings in the fourth month. They are said to
arise in cartilage, which develops in membranous tissue inde-
pendent of the chondrocranium (Hannover, Graf v. Spee).
According to Fawcett (1905), however, the main part of the medial
pterygoid plate is ossified in membrane, although the hamulus is
transformed into cartilage before ossification. According to
Gaupp, there is questionable propriety in applying the term os
pterygoideum to the lamina medialis if thereby one would imply
homology with the os pterygoideum of reptiles. One should prob-
ably homologize it with the lateral part of the parasphenoid.

Each of the lesser wings, orbitosphenoids, is ossified from a
centre which appears in the ninth week lateral to the optic foramen
(Fig. 318, C). On the medial side of each optic foramen a centre
of ossification, presphenoid, appears early in the third month (Fig. j

318, C). The centre for the orbital wing fuses with the corre-
sponding presphenoid centre in the fourth month. The two pre-
sphenoid centres fuse with one another in the eighth month.
Acccording to Hannover (Gaupp, 1906), there are four pre-
sphenoid centres. Toldt and Sutton describe but two.

The presphenoidal centres become partially united to the ba si-
sphenoids in the seventh or eighth month. At birth, however,
there is a ventral wedge of cartilage between the two portions of
the bone. This does not disappear till late in childhood.^^ The
greater wings become joined to the body of the sphenoid during
the first year after birth. The base of the great wing spreads
out over the side of the body of the sphenoid. Between it and the
presphenoid there may be formed a small canalis craniopharyn-
geus lateralis (Sternberg, 1890). Occasionally the hypophyseal
canal persists as a canalis craniopharjTigeus medius.

The posterior end of the nasal septum (crista sphenoidalis
and rostrum sphenoidale) is ossified by extension of bone from
the presphenoid.

The concha sphenoidalis (ossiculum Bertini) arises through

" In many mammals the sphenoid remains permanently divided into two parts,
a presphenoid, which comprises the apical end of the body and the lesser wings,
and a postsphenoid, which comprises the sella turcica, the great wings, and the
pterygoid processes.

MORPHOGENESIS OP THE SKELETAL SYSTEM. 429

ossification of the posterior cupola (Kuppel) of the cartilaginous
uasal capsule (see p. 416). Ossification begins in the fifth intra-
uterine month in the medial (paraseptal) wall of the cupola, and in
the seventh to eighth month a secondary centre arises in the
lateral wall. In the membranous floor of the cupola toward the
end of intra-uterine life further centres of ossification arise and
fuse with the bone originating in the two primary centres. By
the third year each terminal nasal sinus is surrounded by bone
except toward the nasal fossa, where an opening called the
"sphenoidal foramen" persists. Each bone lies on the inferior
surface of the presphenoid, lateral to the crista aphenoidalis and
the rostrum sphenoidale, to which it is united by connective tissue.
About the fourth year the superior and medial parts of the capsule
begin to be absorbed, so that the presphenoid comes to bound the
sinus terminalis. Laterally absorption of the bony capsule also
takes place while the inferior portion and that surrounding the
sphenoidal foramen become fused with the ethmoid. In the ninth
to twelfth year, however, this portion fuses with the sphenoid and
the sinus terminalis extends into the body of the latter (Gaupp,
1906; Cleland, 1863; Toldt, 1882).

OS ETHMOIDALB.

The ethmoid bone arises from one medial and two lateral
primary and from several secondary centres in the cartilaginous
nasal capsule. The ossification of the posterior cupola of the
cartilaginous nasal capsule in man as

the ossiculum Bertini has been de- ibr™

scribed in connection with the sphe- ■■="'

noid bone. In the quadrupeds this
portion of the nasal capsule is ossified
in conjunction with the ethmoid
(Gaupp, 1906). ub^iUS

In each lateral wall of the nasal
capsule a centre appears in the fifth

to sixth fetal month. It gives rise n.cm.ri^'^^iiir'

to the lamina papyracea, and in the eartiiaginoui.i

seventh and eighth months ossification „ ^'°- ^^'>— ('^f"^ ''""^'?i ^^

, . . .? , J IV 1 Renault. f torn Poiri«f.Poiner«.dCharpy,

extends into the conchse and the lam- T™wd'AnBunnie. voi.i. Fig.402.) o»i-
ina eribrosa. The ethmoidal cells are ^('r ."'.■»« of "^^^ '™"' '~^'"'
closed off by folds of mucous mem-
brane which arise in the latter half of fetal life and extend between
the lamina cribro.sa and the upper concha and between the concha'
(Fig. 319). Into these folds of mucous membrane ossification
extends from the concbie so as to give rise to osseous walls for
the ethmoidal cells.

430 HUMAN EMBRYOLOGY.

Ossification begins late in the first year^^ independently in
the superior portion of the nasal septum (lamina perpendicularis).
It extends into the crista galli, the cribriform plate, and the lamina
perpendicularis. Sappey and Poirier, following Rambaud and
Renault, describe several centres on each side of the upper margin
of the lamina perpendicularis at the base of the crista galli. From
these centres ossification extends successively to the crista galli,
the lamina cribrosa, and the lamina perpendicularis. In the crista
galli in the second year a secondary nucleus arises. Ossification
of the process is not completed before the fourth year. In the
second year two accessory nuclei appear in the anterior part of
the lamina cribrosa. By the sixth year the lateral parts of the
ethmoid become united to the medial part (v. Spee and most
authors). ^^ Ossification of the ethmoid is not completed until the
sixteenth year. Synchondrosis exists between the lamina cribrosa
and the sphenoid until toward puberty. About the fortieth to
forty-fifth year the lamina perpendicularis becomes united to the
vomer.

CONCHA INFERIOR.

This arises in cartilage from a separate centre of ossification
which appears in the latter half of fetal life (seventh month,
Toldt; fifth month, Quain, Graf v. Spee).^*

VOMER.

The vomer arises from a bilaterally placed pair of nuclei
which appear during the eighth week (Quain, Mali), near the back
of the inferior margin of the cartilaginous nasal septum. These
centres unite beneath the inferior margin of the septum, but
superiorly they extend on each side of the nasal septum so as to
enclose the cartilaginous septum between two thin plates of bone.
The two plates of bone gradually become coalesced from behind
forwards. Union is completed about the age of puberty (Quain).
On the anterior and superior margins a permanent groove remains
for the attachment to the lamina perpendicularis ossis ethmoidalis
and the cartilago septi nasi. Although the vomer develops on
each side of the cartilaginous nasal septum and at its expense, it
is regarded as a true membrane bone.

81
S3

According to v. Spee, before birth.

The lamina cribrosa ossifies in part through extension of ossification from
the crista gnWi and from the lateral ossific centres and in part from accessory
centres. According to Sappey, Poirier, Toldt, and some other authors, the central
part of the ethmoid becomes united to the lateral parts through ossification in the
lamina cribrosa at the end of the first or in the second year.

"Third or fourth month after birth (Sappey, Testut, Poirier).

MORPHOGENESIS OP THE SKELETAL SYSTEM. 431

OS PAIiATINUM.

The OS palatinum (a membrane bone) arises from a single
centre of ossification which appears in the eighth week (KoUiker,
Le Double, Mall, Fawcett) in a region corresponding with the
angle between the horizontal and vertical parts, or, according to
Fawcett, in the region of the vertical plate. Bambaud and Renault,
Sappey, Cruveilhier, and others describe two or more centres. The
vertical part extends upwards on the medial surface of the lateral
wall of the cartilaginous nasal capsule and by this is separated
for some time from the maxilla. It extends between the carti-
laginous inferior and middle conchae and the cartilaginous lateral
wall of the nasal capsule, thus separating the posterior extremi-
ties of the former from the latter. The pars horizontalis appears
much earlier than the processus orbitalis and the processus
sphenoidalis.

OS NASALE.

This is a membranous bone which develops on the surface of
the cartilaginous nasal capsule. The underlying cartilage is still
present at birth, but subsequently becomes absorbed. It is usually
stated that there is a single centre of ossification which appears
at the end of the second month. Zuckerkandl (1895) has suggested
that the anomalies of development shown by the nasal bone indi-
cate that it may arise at times from two or even three centres of
ossification. According to Perna (1906), the nasal bone arises
from two anlages, a lateral membranous and a small medial car-
tilaginous. Remnants of the suture between the two may exist as
an incisura nasalis.

OS LACRYMALE.

This is a membrane bone which arises on the lateral wall of
the posterior part of the cartilaginous capsule of the external nose.
The centre of ossification appears in the third month (83d day.
Mall). The facies lacrjinalis ossifies first, then the crista and
hamulus, and lastly the facies orbitalis. In the adult the bone
varies greatly in form (see MacAUister, v. Spee, Zabel, Le Double,
etc.). Occasionally the bone in the adult is bipartite, indicating
an accessory centre of ossification.

OS TEMPORAL.E.

The human temporal bone is the result of the fusion of several
distinct elements, petrosal (periotic), squamosal, tympanic, tym-
panohyale, and stylohyale. In addition it encloses the three bones
of the middle ear. At birth it consists of three pieces, a squa-

432 HUMAN EMBRYOLOGY.

mosum, a petrosmn and a tympanieum. These become fused
together during the first year.

The squamosum (Figs. 320, 321) is ossified from a single
centre of ossification which appears in the membranous tissue in
the region near the base of the zygomatic process of the squama
{Mall, 1906).** From the posterior part of the squamosum a
post-auditory process grows downwards beneath the region of
the linea temporalis between the tympanic and petrosal portions
of the bone. It forms the superior anterior part of the mastoid.
The squamosum encloses laterally the cavnm tympani and the
antrum mastoideum, from which the mastoid cells subseqaentlj-
develop."

FlQ. 3^0.— <AIUr Ssppey. Tni

The tympanieum (Figs, 320, 321, 324) is a membrane bone.
Its centre of ossification appears toward the end of the third month
in the anterolateral part of the external membranous wall of the
cavum tympani, near the angle between the capitulum of the mal-
leus and Meckel's cartilage. It has a concave surface turned
toward the latter. From this centre a band of bone grows first
downwards, medialwards, and backwards and then upwards and
lateralwards so as to form a semicircular bone surrounding the
tj-mpanic membrane. In the tenth fetal month first the free ends
of the bone fuse with the squamosum and then the under part fuses
with the petrosum. By addition of osseus tissue to the lateral

" According to Rambaud and Renault, Toldt, Poirier, and others, tbe squa-
mosimi arises from three centres of ossification, one at the base of the zygomatic
process, one in the squamosa, above this, and one behind the tympanieum. AmODg
the variations found in tlie squamosal portion of the temporal bone are a division
iiito a superior and an inferior part or into an anterior and a. posterior part.

"Fiichs (li)05-l£)07), chiefly from the study of rabbit embryos, has come
to the conclusion that the squamosum of mammals is composed of three parts, a
I and a zygomatic (quadrato-jupale) part, each ossitied in membrane,
articular part prefomjed in cartilajre (pars artieularis quadrati).

MORPHOGENESIS OF THE SKELETAL SYSTEM. 433

and medial margins of the bone, the primary narrow band becomes
converted by the third year into a broad rolled-up plate of bone,
which medially forms the ventral wall of the cavnm tympani and
laterally the ventral wall of the meatus acusticus estemus. At
this period the inferior surface of the tympanicum presents an
aperture of some size which usually but not always becomes closed.
According to Rambaud and Renault, Hammar, and others, the
bone arises from several centres of ossification.

ahown. The pi

Tympanohyale (laterohyale) and stylohyale. See p. 439.

The periotic portion, os petrosum {Fig. 322), arises from the
ossification of the cartilaginous otic capsule. There are several
centres of ossification, Tliese centres arise during the fifth month
and become fused with one another in the sixth. The descriptions
of the centres of ossification in the labyrinth given by various
authors differ considerably. That of Vrolik, as adopted by Gaupp
(1906), is here chiefly followed. The first centre to appear is one
in the region of the promontory between the fenestra vestibuli and
the fenestra cochleae in a fetus 17 cm. long. Ossification extends

Vol. I.— 28

434 HUMAN EMBRTOLOQT.

from here around the fenestra vestibuU and forms that part of
the petrous bone which lies below the poms aousticus iDtemus and
the fenestra cochlearis. A second centre appears on the dorso-
lateral surface of the central paf t of the capsule over the superior
semicircular canal. Ossification extends from this into the region
of the processus perioticus superior. It forms most of the
cranial surface of the petrous bone, gives rise to the superior

boundaries of the internal auditory meatus and the fenestra
cochlearis, and also to a portion of the superior medial part of
the mastoid. A third centre arises at the anterior proximal part
of tlie cochlea near the incisura pro-otica. More caudally, medial
to the fossa subarcuata, there arises a fourth centre of ossification.
The fifUi centre appears on the outer surface of the posterior part
of the capsule in the region of the posterior semicircular canal ;
the sixth centre arises slightly in front of the fifth. From the last

MORPHOGENESIS OF THE SKELETAL SYSTEM. 435

two centres ossification extends into the parietal plate and the pars
mastoidea of the tectum posterius. At the end of the sixth month
the labyrinth is completely enclosed by bone.

The tegmen tympani is ossified partly in membrane, partly
in the cartilage of the processus perioticus superior by extension
from the periotic capsule. There is occasionally found in man a
separate bone in the anterior part of the tegmen tympani. This
perhaps represents the ossiculum accessorium malleoli, which in
some mammals has an independent centre of origin on the upper
side of the proximal end of Meckel's cartilage (van Kampen,
1905).

The embryonic epithelial labyrinth at first lies in a cavity
surrounded by cartilage. The inner surface of this cartilage
becomes transformed into membranous tissue, and this in turn
in part furnishes a membranous covering for the labyrinth, and
in part becomes ossified, forming the inner lining of the bony
labyrinth, including the modiolus, the lamina modioli, and the
lamina spiralis ossea. (See Kolliker, 1879; Bottcher, 1869.)

The canalis caroticus is represented by a slight groove in.
the cartilaginous skull. It becomes converted into a canal during
the period of ossification. At birth the central part only is roofed
over.

Between the apex pyramidis and the sphenoid a part of the
chondrocranium persists as the fibrocartilago basalis, which lies
in the foramen lacerum.

Formation of mastoid cells does not begin until after birth,
but in the second year they extend from the antrum into the
mastoid process.

The Canalis Facialis. — The short facial canal in the chondro-
cranium is equivalent merely to the first part of the facial canal
in the adult (part from the porus acusticus int. to the region of
the geniculate ganglion) . Before the chondrocranium is replaced
by bone the nerve passes out from the canal above mentioned, then
beneath the crista parotica and over the stapes, and thence back-
wards and downwards beneath the tympanohyale, and then out-
wards and ventralwards toward the surface of the body (Fig. 311).
The nervus petrosus sup. major leaves the main trunk near the
lateral orifice of the cartilaginous canaP® and runs forward on
the lateral wall of the capsule. The chorda tympani separates
from the main trunk behind the stylohyale, runs forwards lateral
to this cartilage and then between the malleus and incus. It is not
enclosed in a canal in the chondrocranium. When the lateral wall
of the auditory capsule becomes ossified, the facial nerve is en-

" In the human fetus and in Talpa through a special opening in the external
orifice of the facial canal (E. Fischer).

436 HUMAN EMBRYOLOGY.

closed at first in a groove and later in a canal. While the facial
nerve is being enclosed bony lamellae likewise enclose the stape-
dius muscle and the chorda tympani. The facial nerve and
Eeichert's cartilage may be looked upon as caught between the
tympanicum and the mastoid part of the petrosum, the chorda
tympani and Meckel's cartilage as caught between the tympanicum
and the squamosum, the tuba auditiva (Eustachii) as enclosed
between the tympanicum and the pars cochlearis of the petrosum
(van Kampen).

OS PAKIETAXiE.

The parietal arises as a membrane bone from two centres
(Toldt), a superior and an inferior, which soon fuse into a single
centre which lies in the region of the tuber parietale. The centres
appear toward the end of the second month and apparently some-
times arise as a single centre. The ossification radiates outwards
from the combined centre of ossification toward the sphenoidal
and occipital angles, so as to give rise for a time to an hourglass-
shaped plate of bone (Mall). At a later period a notch is left in
the sagittal margin of the bone in front of the occipital angle.
The notches of the bones of the opposite sides together form the
sagittal fontanelle, which toward the end of fetal life usually
becomes closed, but may sometimes be recognized after birth.

OS FRONTALE.

This has two centres of ossification, one on each side of the
body in the region of the tuber frontale (Fig. 321). These centres
arise toward the end of the second month (56th day. Mall). From
each a lateral half of the bone is formed. The orbital part of the
bone appears in the ninth week. Toldt found no secondary centres,
but these have been described by Rambaud and Renault, Serres,
Jhering, v. Spee, and others. These accessory centres include, on
each side of the bone, one for the spina trochlearis, one for the
processus zygomaticus, one for the posterior part of the orbital
region, and one which arises late in the spina frontalis lateral to
the foramen caecum. The two lateral halves of the bone are sepa-
rated at birth, but during the first year become approximated in
the midsagittal line. The middle part of the frontal suture becomes
ossified in the second year. By the eighth year the suture is
usually obliterated except inferiorly. Near the root of the nose
the frontal suture is sometimes widened to form a fontanella
metopica, in which an os metopicum may be formed. Ossicles may
appear also in other parts of the frontal suture (Schwalbe, 1901;
Fischer, 1901). The frontal sinuses begin to be developed early
(first year, Toldt), but develop very slowly until toward puberty.
They increase in size until late in life.

MORPHOGENESIS OP THE SKELETAL SYSTEM.

437

FONTANEU^S.

The chief fontanelles are spaces covered by membranes which
lie between the incomplete angles of the parietal and the neigh-
boring bones.^^ The anterior fontanelle (fonticulus frontalis) is
situated between the frontal angles of the parietal and the postero-
superior angles of the two parts of the frontal bone. It remains
open until the third year. The posterior fontanelle (fonticulus
occipitalis) is situated between the occipital angles of the parietal
bones and the superior angle of the occipital. This fontanelle at
birth is nearly obliterated, but the bones which bound it are still
separated by membrane and are movable. It becomes closed
between the third and sixth month. The lateral fontanelles (fon-
ticulus mastoideus, fonticulus sphenoidalis) are situated between
the sphenoidal and mastoidal angles of the parietal and the neigh-
boring bones. The fonticulus mastoideus closes during the first
half of the second year, the fonticulus sphenoidalis in the third
year. The flat bones of the skull are united by definitive sutures
by the end of the fourth year.^^ Special small bones (Wormian
bones) may develop in the fontanelles during the process of
ossification.

MAXILLA.

The human maxilla consists of two distinct parts, a medial,
the incisivum (premaxilla) of lower forms, and a lateral, or
maxilla proper. According to Mall (1906), each of these parts of
the bone ossifies from a single centre. The two centres appear at
the end of the sixth week and become united at the end of the

Sulcus lacrimalis
maxillaris fH^

Os .

iDcisivum

Processus '
palatinus

Sutura

ineisiva
f

^^^S^SrjdC S"**^°^*

^ _ProceBgug
HGT^ al veolaris

f^S^^^**^*"* .«^U«4Mr

WWTa

HL

\3k^W^

Processus Os
palatinus incisivum

)^^

A B

Fig. 323.— (After Toldt, Anat. Atlas, 1900, Heft 1, Figs. 176. 177.) The left maxilla of a fetus 30 cm. long.

A. Medial surface. B. Inferior surface.

second or early in the third month. Each of the centres gives rise
to a part of the frontal process. The alveolar borders of the
two bones unite before the frontal processes do. Authors differ
greatly in the number of centres which they ascribe to the bone.
The number given varies from two to six. Hertwig's model and

"For an a<?count of the transitory sagittal fontanelle between the parietal
bones see above under Os parietale. For the metopic fontanelle see above under
Os frontale.

" For the time and order of closure of the chief fontanelles see Adachi (1900).

438 HUMAN EMBRYOLOGY.

Schultze's illustration of the bones of the skull of an embryo of
the third month are cited by Mall in support of his own
observations.^®

At first the maxilla lies lateral to the cartilaginous nasal cap-
sule. Aiter this cartilaginous capsule is in large part absorbed
the maxilla helps to bound the nasal cavity, the maxilloturbinale
becomes joined to it, some of the ethmoid cells are closed off by it,
and the sinus maxillaris is formed. The formation of the alveolar
process begins in the fourth fetal month and is completed after
the twentieth year. According to Mihalkovics (1899), the proc.
paranasalis of the nasal capsule is caught up in the ossifying
maxilla. This is said to account for the islands of cartilage some-
times described in the ossifying maxilla.'*® The infraorbital nerve
and vessels lie at first in a groove on the orbital surface of the
maxilla, but later become enclosed by a lamina of bone which
extends upwards on the lateral side, and then bends medialwards
(see Fig. 321). The lateral part of the floor of the orbit and the
infraorbital nerve lie at first very near the alveolar process of
the maxilla. The development of the sinus maxillaris gradually
serves to separate them. Compare the maxilla shown in Fig. 321
with that of an adult skull.

The sinus maxillaris at birth is represented by a slight
depression on the medial surface of the maxilla opposite the second
molar. After birth this depression extends laterally into the
maxilla beneath the groove of the infraorbital nerve and blood-
vessels. After the second dentition the sinus becomes greatly
enlarged.

OS ZYGOMATICUM.

This appears on the 56th day as a small, three-cornered centre
in the membranous tissue beneath and lateral to the eye (Fig.
321). On the 58th day it is four-cornered. Two of the comers
give rise to processes partially encircling the orbit, one of the
others extends to the maxilla, and one toward the temporal bone
(Mall, 1906). From this period on, the adult form of the bone is
steadily approached.**

"According to Le Double (1906), the number of centres described by various
authors for the maxilla, including: the incisivum, is as follows : One, Camper, Rous-
seau, Cleland; two, Jamain ; three, Serres, Meckel, Cruveilhier; five, B6clard, Sappey,
Leidy, Poirier, W. Krause; five or six, Portal; six, Rambaud and Renault; seven,
Weber.

** In fetuses of the fourth to fifth month there may arise in the alveolar part
small cartilaginous islands which have no connection with the nasal capsule and
which disappear during the ossification of the upper jaw (Gaupp, 1906).

*^In the adult partially or completely bipartite and tripartite malar bones
are not very infrequent. In the Japanese and Ainos there is found a considerable
percentage of skulls in which the malar bone is partially or completely divided by
a horizontal suture (os Japanicum, os Ainoicum). Various writers differ greatly

MORPHOGENESIS OF THE SKELETAL SYSTEM. 439

AUDITORY OSSICLES.

These begin to ossify during the last half of the fifth month.

The malleus has a centre of ossification from which all parts
of the bone arise except the processus anterior. This centre arises
in the upper part of the coUum and from here ossification spreads
to the other parts. The manubrium, the last part of the bone to
become ossified, reaches its definitive form before birth. The
processus anterior (Folii) arises at the end of the second month
as a slender membrane bone on the medial side of Meckel's car-
tilage. It reaches its definite length in the middle of the sixth
month. The proximal end fuses with the collum mallei toward
the end of the fifth month (Broman), at the time of ossification of
the latter. When the malleus is ossified it becomes clearly demar-
cated from the rest of Meckel's cartilage. The latter slowly
atrophies, and is replaced by connective tissue, which first appears
at its periphery.

The incus is ossified from a single centre which appears in
the upper part of the crus longum. Ossification extends from
here into the other parts of the bone, including the processus len-
ticularis. The ossification begins in fetuses 19-20 cm. long and
by the time of birth has reached its definitive extension (Broman).

In the stapes, a centre of ossification usually appears in the
basal portion in fetuses 21 cm. long (Broman). From this centre
the bone is ossified. The capitulum is usually ossified by the end
of the sixth month.

TYMPANOHYALE.

The tympanohyale is probably derived from the cartilaginous
tympanohyale described in connection with the chondrocranium,
although tympanohyale and stylohyale are fused before ossifica-
tion appears. Late in fetal life it is ossified from a special centre
and becomes included between and fused to the petrosum and the
tympanicum. It helps to bound the tympanic cavity medial to the
OS tympanicum.

in the number of centres of ossification which they ascribe to the bone. Le Double
(1906) classified these writers as follows:

Those describing one centre of ossification: Meckel, Beclard, Hyrtl, Sappey,
Cruveilhier, Jamain, Leidy, Baraldi, Lachi, Romiti, Langer-Toldt, Stieda, Merkel,
Graf V. Spee, Hartmann.

Those describing one or two centres: Parker and Bettany.

Those describing two centres : Kerckring, Lieutaud, Garbiglietti, Macalister.

Those describing two or three centres : Morris and Rauber.

Those describing one, occasionally two, rarely three : Breschet, Gruber.

Those describing one, occasionally three : Virchow, Albrecht, Testut, Thane.

Those describing three centres : 0. Schultze, Kollmann, Frassetto, Minot, Spix,
Calori, Quain, Rambaud and Renault, Schrenck, Poirier, Kolliker, C. Toldt, Le
Double.

440 HUMAN EMBRYOLOGY.

STYLOHYALE.

The cartilaginous stylohyale gives rise to the styloid process.
This ossifies after birth and is usually united to the tympanohyale
by cartilage until middle age when it may become united to the
latter by bone (Flower, 1870).

KERATOHYALE.

This is derived from the proximal part of Reichert's cartilage.
It gives rise to the stylohyoid ligament. Occasionally it may
become ossified and fused to the stylohyale and the lesser comu
of the hyoid.

OS HYOIDEUM.

This has five primary centres of ossification, — one for the body
and one for each of the greater and each of the lesser comua.
Ossification begins in the body and greater comua late in fetal life ;
in the lesser comua some time after birth. The greater cornua and
body unite in. middle life. The lesser comua are united by bone to
the body of the hyoid only rarely. Usually a cartilaginous union
remains throughout life. According to Eambaud and Renault,
the centre in the body arises by fusion of two bilaterally placed
centres. After puberty secondary centres for the tips of the
greater comua are described (Poirier, Traite d'Anatomie).

MANDIBLE.

This is ossified in the membranous tissue lateral to Meckel's
cartilage. The centre of ossification may appear as early as the
39th day. By the 42d day the ramus and alveolar process may
be distinguished. In a fetus 55 days old the beginnings of
the coronoid process and condyle are visible. Before the end of
the second month sockets for the teeth may be distinguished. By
the middle of the third month the mandible has reached its char-
acteristic shape (Mall, 1906). ^^ During the development of the
mandible cartilage is produced in the membranous tissue of the
tip of the condyle, in the angulus, the proc. coronoideus (see
Fawcett, 1904; Low, 1905), and, according to Henneberg, in traces
also on the superior lateral and the medial alveolar margins and
the inferior lateral margin of the jaw. This cartilage* has nothing
to do with Meckel's cartilage. From Meckel's cartilage, however,
there may be derived the cartilage in the symphysis of the jaw
in which small bones, ossicula mentalia, develop in the eighth
month. There are usually two pairs, or one unpaired bone and one
pair of bones. They lie in the lower portion of the symphysis

" Several investigrators, among whom may be mentioned Rambaud and Renault
and Wolff (1888), describe several centres of ossification for the mandible.

MORPHOGENESIS OP THE SKELETAL SYSTEM. 441

and after birth become fused to the mandible and help form the
protuberance of the chin; see v. Mies (1893), Toldt (1905-6),
V. Bardeleben (1905). According to Low (1905), Meckel's car-
tilage near the incisors becomes ossified and fused to the mandible.
According to Fawcett (1904), Meckel's cartilage becomes ossified
from the foramen mentale to the median line. The ossified carti-
lage becomes enclosed in membrane bone. At birth the lower jaw
usually consists of lateral parts united at the symphysis by fibrous
tissue. Osseous union takes place in the first or second year after
birth.

Hutubrium dullei
Fici, 324,— (A(t«r KoU

TEMPOBOMANDIBULAB JOINT.

This joint is developed between the membrane which covers
the condyle of the mandible and the periosteum of the squamosum.
In the loose tissue between the two a condensation marks
the beginning of the differentiation of the discus articularis.
On each side of this discus a joint cavity develops. Each joint
cavity is throughout life lined by fibrous tissue. Beneath the joint
periosteum of the mandible and of the temporal bone a thin layer
of cartilage is produced (see Kjellberg, 1904). According to
Walliseh (1906), in the new-bom the tubereulum articulare is
still undeveloped and the condyle is flatter than in the adult. The
condyle reaches its definitive form and the tubereulum is devel-
oped after the teeth appear.*^

"According to Fuebs (1905), tbe temparomandibular joint in rabbits, and
hence by inference in other mammalB, is homolt^^us witb the quadra to-articular
joint of reptiles. As mentioned above, following Reiehert, most investigators have
eome to the conclusion that the reptilian quadra to-articular joint is represented in
mammals by tbe joint between the malleus and incus, while the temporomandibular
joint of mammals is phylogenetieally a new structure, a squamosodental joint. (See
Gaupp, 1906.)

442 HUMAN EMBRYOLOGY.

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XIL

THE DEVELOPMENT OF THE MUSCULAR

SYSTEM.

By warren H. LEWIS, Johns Hopkins University, Baltimore, Md., U. S. A.

The entire musculature, both cross-striated and smooth, with
a few exceptions that are of ectodermal origin, arises from the
mesoderm. Since contractility is a fundamental property of all
cells it is not surprising that the ectoderm as well as the mesoderm
should give rise to cells in which this function is highly developed.
The ectoderm of the optic cup undoubtedly gives rise in most
vertebrates, probably in all, to ,the musculus sphincter and the
musculus dilatator pupillae: Nussbaum (1900, 1902), Herzog
(1902), Heerfordt (1900), Szili (1901), Lewis (1903), Collin
(1903). In mammals these muscles are of smooth fibres, but in
birds and reptiles of cross-striated fibres. The muscles of the
glandulse sudorifera? are also of smooth muscle derived from the
ectoderm: Ranvier (1889), Koelliker (1889), Stohr (1902),
Heidenhain (1893).

The mesoderm, however, gives rise to the great bulk of the
musculature, both smooth and cross-striated. The smooth and
cross-striated muscles are not to be considered as fundamentally
diif erent ; they represent different grades of development of con-
tractile tissue or different paths of differentiation from a common
fundamental form. The smooth muscle shows a lower grade of
differentiation. In insects and birds, for example, portions of
the intestinal tract are supplied with cross-striated muscle, while
in mammals the corresponding regions are supplied by smooth
muscle. Marchesini and Ferrari (1895) found that in early de-
velopment smooth and striped muscles show exactly the same
structure. The fact that the myotomes give origin to many of
the cross-striated muscles does not distinguish this variety from
the smooth muscle, inasmuch as many of the cross-striated muscles
— in the head, for example — arise directly from the mesoderm
quite independently of the myotomes and in a manner similar
to the origin of the smooth muscle.

It has been customary to consider the voluntary musculature
as being derived almost entirely from the primitive segments;
yet in mammals the attempts to homologize the head muscles

454

DEVELOPMENT OF THE MUSCULAR SYSTEM. 455

with those of the trunk derived from the myotomes have failed,
as there are no indications of preotic segments in the head
region; the head muscles develop directly from the mesoderm of
the branchial arches and the dorsal eye region. The muscles of
the limbs likewise arise directly from the mesoderm of the limb
buds; but here uncertainty still exists as to what role migrating
cells from the myotomes may play in their development. The
muscles derived directly from the myotomes — namely, the deep
muscles of the back and the intrinsic thoraco-abdominal mus-
culature— ^are to be considered as both phylogenetically and on-
togenetically the oldest of the skeletal muscles. The skeletal
muscles of the head and limbs are, on the other hand, of later
origin, and probably not derived from the more primitive seg-
mental musculature, but directly from the mesoderm. Until, how-
ever, we have a more complete picture of the developmental
history, not only in mammals but also in the lower vertebrates,
the relationships must remain obscure. The development of many
of the muscles in man and mammals has never been traced, and
of the remainder our knowledge is fragmentary and incomplete.
It has commonly been supposed that the first differentiation
of the muscles from the mesoderm takes place under the influence
of the nervous system through the agency of the motor nerves,
and that self -differentiation of muscles does not occur. Such a
belief arose from our knowledge of the very early union of the
motor nerves with the developing myotomes and muscle masses.
Teratological evidence is at present conflicting. Neumann (1891),
from his studies of acephalic and amyelic monsters, concludes
that the influence of the motor nerves is necessary for the dif-
ferentiation of the muscular system. Leonowa (1893) and Fraser
(1895) have described human monsters without brain and spinal
cord in which the peripheral sensory nerves and musculature
were normally developed. On the other hand, E. H. Weber (1851),
Neumann (1901), and others have described cases in which ab-
sence of certain portions of the central nervous system has been
accompanied by total absence of musculature which is normally
supplied by the lacking nerves, although skeleton, blood-vessels,
and even tendons were normally developed. Neumann would rec-
oncile these apparent differences by assuming that muscles first
arise under the influence of the nervous system, but that their
nourishment and further growth during the embryonic period
take place independently of the central nervous system, and not
until the post-embryonic life is reached is the dependence again
established. Thus, the nervous system must have developed in
the early stages of embryonic life up to a certain point and under-
gone degeneration after differentiation of the muscular system
had taken place. Herbst (1901) concludes, from the same data,

456 HUMAN EMBRYOLOGY.

that the sensory nerves, including the cells of the spinal ganglia,
and not the motor nerves, are necessary to stimulate the dif-
ferentiation of the muscular substance in the embryo. The well-
known fact that a muscle undergoes atrophic changes after its
nerve supply has been cut off would at first sight uphold the
view that the influence of the nervous system is necessary for
the differentiation of contractile tissue. The study of the normal
development likewise affords some evidence which might be in-
terpreted as tending to support it, though it does not necessarily
do so. In the embryos of lower vertebrates, for instance, the
connection of the motor spinal nerves with the muscle plates is
established just at the time when the contractile substance begins
to be laid down, but in the pig embryo, according to Bardeen
(1900), the musculature is differentiated to a considerable extent
before the nerves establish a connection with it: Harrison (1904).
It was only by the experimental method on the lower verte-
brates that this question seems to have been finally settled,
especially by the brilliant work of Harrison (1904). Harrison
removed the spinal cord in a series of frog embryos before the
histological differentiation in either the muscular or nervous
system had begun, so that from the very beginning isolation of
the musculature from the nervous system was complete, and all
chance for the exertion of any peculiar formation stimulus emanat-
ing from the nervous system as such was eliminated; and like-
wise, owing to the consequent paralysis of the muscles in question,
any possible stimulus resulting from the functional activity of
the muscle itself was excluded. Still the differentiation of the
contractile substance took place in the normal manner, as did the
grouping of fibres into individual muscles. It is not likely that
the conditions in mammals and man differ from those of the frog.
Thus it is seen that all the constructive processes involved in
the production of the specific structure and arrangement of the
muscle-fibres take place independently of stimuli from the nervous
system and of the functional activity of the muscles themselves.
Cross-striated muscle tissue and the indi\adual muscles are thus
self-differentiating. At a later period during functional activity,
as the experiments of severing the nerve to a muscle show, the
muscle becomes dependent on the influence of the nervous system
for its continued normal existence, either through a trophic in-
fluence or functional actiA^ty. At how early a period in the de-
velopment of the ovum this power of self -differentiation of mus-
cular tissue begins can be but problematical. Lewis (1907) found
that in the early gastrula stage of the frog, tissue in the lips of
the blastopore possesses the power of independent differentiation
into muscular substance. Thus it appears that muscle tissue is
already predetermined in the early gastrula. It is probable that

DEVELOPMENT OF THE MUSCULAR SYSTEM. 457

this predetermination exists much earlier, even in the egg itself.
Conklin (1895) has been able to determine in ascidian eggs, even
before cleavage begins, the existence of organ-forming substances,
one of which, the myoplasm, that has to do with the formation
of muscle tissue, is clearly recognizable and can be followed
through successive stages of development into formed muscle.

Harrison's experiments likewise show that the formation of
the individual muscles from the myotomes and muscle complexes
takes place independently of the nervous system. It has often
been assumed that this splitting up of the complex muscle masses
into the individual muscles has come to pass through the active
ingrowth of connective tissue, blood-vessels, and nerves. There
is, however, no experimental evidence indicating that either the
connective tissue, the blood-vessels, or nerves take an active part
in this process, although descriptive observation might readily
lead one to such a conclusion. It is more probable that the ex-
planation lies primarily within the muscle mass itself and secon-
darily to the relations which the muscle masses may have to
shifting skeletal elements. Harrison's experiments would also
eliminate functional activity as a necessary factor in this forma-
tion of individual muscles.

Although the nervous system does not influence muscle dif-
ferentiation, the nerves, owing to their early attachment to the
muscle rudiments, are in a general way indicators of the position
of origin of many of the muscles, and likewise in many instances
the nerv^es indicate the paths along which the developing muscles
have migrated during development: Mall (1898), Nussbaum, Bar-
deen and Lewis (1900), Lewis (1902), Bardeen (1907), Futamura
(1906), Grafenberg (1905). The muscle of the diaphragm, for
example, has its origin in the region of the fourth and fifth cervical
segments. The nervus phrenicus early enters the muscle mass
and is carried with the muscle in its migration through the thorax.
The Mm. trapezius and sternocleidomastoideus arise in the lateral
occipital region as a common muscle mass, into which at a very
early period the nervus accessorius extends, and as the muscle
mass migrates and extends caudally the nerve is carried with
it. The Mm. pectoralis major and minor arise in the cervical
region and receive their nerves while in this position; then the
mass migrates caudally and ventrally over the thorax. The Mm.
latissimus dorsi and the serratus anterior are excellent examples
of migrating muscles whose nerve supply indicates their origin
in the cervical region. The M. rectus abdominis and the other
muscles of the abdominal wall migrate or shift from a lateral
to a ventrolateral or ventral position, carrying with them the
nerves. The nervus facialis, which early enters the common facial
muscle mass of the second branchial arch, is dragged about with

458 HUMAN EMBRYOLOGY.

the muscle as it spreads over the head and face and neck, and
the nerve splits into its divisions parallel with the splitting of
the muscle mass into its various muscles.

The nerve supply serves in part as a key to the common origin
of certain groups of muscles. The nervus oculomotorius enters
in the early embryo a common muscle mass which later splits
into various eye muscles supplied by it. The nervus trigeminus
first enters the common muscle mass in the mandibular arch which
later splits into the various muscles supplied by this nerve and
its branches. The lingual muscles arise from two muscle masses
which are supplied by the two hypoglossal nerves. The infra-
hyoid muscles arise from a common mass supplied by the ramus
descendens nervi hypoglossi. The M. trapezius and the M. sterno-
cleidomastoideus arise from a single mass.

Where a muscle is supplied by nerves from two or more
segments, the indication is that such muscle has had a complex
origin, as the Mm. rectus abdominis, obliquus extemus and in-
ternus ; but this is not always the case, for a muscle may receive
secondarily new nerves, retaining at the same time its original
nerve, as the M. trapezius, which was originally supplied only
by the nervus accessorius and later receives branches from the
cervical plexus. The M. digastricus also is, according to Futamura
(1906), at first entirely supplied by the nervus facialis, later, as
the anterior belly becomes constricted off from the posterior, the
former obtains its motor nerve secondarily from the nervus mylo-
hyoideus.

The site of entry of a nerve into the muscle, as a rule, marks
the region of earliest differentiation (Bardeen, 1907), and in
many instances at least the distribution of the nerve within the
adult muscle indicates the course of development or growth of that
muscle (Nussbaum, 1894).

HISTOGENESIS.

Smooth Muscle. — We have already noted that smooth muscle
may arise either from the ectoderm or the mesoderm; the great
bulk of smooth muscle, however, arises in situ from the mesoderm,
either directly from the mesenchymal derivatives of the meso-
derm or from embryonal connective tissue. The various
stages in its histogenesis from the mesoderm have never been
carefully traced in man, and the following account is based on
the excellent work of McGill (1907) on the histogenesis of the
smooth muscle in the alimentary canal of the pig.

The mesenchyme which arises from the mesodermal germ
layer is in the form of a syncytium, with protoplasmic continuity
throughout the entire syncytial mass. ** The nuclei of the

DEVELOPMENT OP THE MUSCULAR SYSTEM. 459

syncytium are round or oval, with distinct nuclear walls and
heavy chromatin reticulum." *' The protoplasm shows a fine
reticular structure, the strands of the reticulum being made up
of rows of fine granules " (Fig. 325). This syncytium persists
throughout intra-nterine life and even in the adult. "Separate
and distinct smooth mnscle-cells or fibres do not exist at any
stage of development." Thus the term "cell" as here used refers
to the enlarged, thickened por-
tion of the syncytium surround-
ing the nucleus. "Before muscle
development begins, there is a
general condensation of the mes-
enchyme," with multiplication of
the cells, followed by marked
. elongation of the nuclei in the
region in which muscle is to
differentiate. Not all smooth
muscle develops from this prim-
itive mesenchyme, for in later
stages the muscle comes from the
more developed mesenchyme or
embryonal connective tissue. In
the alimentary tract, for example,
the longitudinal muscle appears
much later than the circular and
arises from the embryonal con-
nective - tissue syncytium into
which the primitive mesenchyme
has been transformed. "In the
areas of muscle formation not all
of the mesenchymal cells (or, in

later development, of the em- i.itj.

bryonal connective-tissue cells)
elongate; some retain their stel-
late shape, with oval nuclei, and
from these, in later development,
mnscle-cells may arise; but they form in the main the anlage
of the interstitial connective tissue."

"As the elongation of mesenchymal and connective-tissue
nuclei continues, in the formation of muscle tissue, there is an
increase in the amount of protoplasm surrounding each nucleus.
The perinuclear protoplasmic masses also elongate, corresponding
to the nuclei, so that the cells change from stellate to spindle-
shaped," without, however, losing the protoplasmic bridges which
unite the entire mass into a syncytium; in fact, the bridges be-
come larger in places. During the earliest stages the muscles

Fra. 325.— (AlWi MeCiH: Inl«ii«t.

■ch, f. Anat. u. Phys.. Tsl. vii. Fig. 1.)

' (Esophsaug of a 7-mm. pig, Bhowing <w

460 HUMAN EMBRYOLOGY.

increase in size by additions from and transforniation of the
mesenchymal cells. Mitosis is abundant in the mesenchj'me and
rare in the developing muscle. During the second period, in which
the muscles are differentiating by the rapid formation of myo-
fibrills and increase in the size of the elongated nuclei, there is
little formation of new muscle tissue. Still later there is a second
period of muscle growth in the circular layer of the cesophagus,
which continues until the adult form is reached. "This increase
is apparently due to two factors, — first, differentiation of the em-
bryonal connective tissue both at the margins of the already

Pia. 326.— (After McOil!: InUraat. Uantsmch. t. Anat. u. Phyi.. 24, Tmt. vii, Pig. 3.) From Iha
(eeoph(4(UB of a 13-mm. pig, showinn markEd Elonaaiion of me»«tichym»l eellb and nudd, with Ibe form*-
tJon of coarse myoBbrillie (/c), gnmular ppindle {ff*\ Eranulee fuaed into a homofeneous npindle (Ac),
anil their ead-to-eud union (At), mesenchymal ceLls (m), intimately coDDected witli mUBd*-ceUe.

formed muscle layer and also apparently of that lying between
the muscle elements, and second, by the mitotic division of the
already formed muscle nuclei,"

"Immediately following the process of elongation of the
mesenchyme, or in later stages of the embryonal connective tissue,
the myoflbrillje are fonned in the protoplasm of the elongating
cells or nuclear masses" (Fig. 326). "There are two kinds of
myofibrilliE, coarse and fine." "The coarse myofibrillte are the
first to develop." "The protoplasm of the stellate mesenchyme
appears to contain a granular reticulum," and, as the cells
elongate to form muscle, the granules increase in number and
take a more intense stain than the ordinary protoplasm. "As

DEVELOPMENT OF THE MUSCULAR SYSTEM. 461

tlie elongation continues, the granular fibrils of the protoplasmic
reticulum are stretched out more and more, and finally appear as
more or less distinct longitudinal strlations" {Fig. 327). "The
protoplasm of the cell body appears to be made up largely of

Y.f.

Fio. 327. — (After MeCiill; laWmBt. Monat. f. Anst, u. Phys.. 24. Fi(. 8, Ttl. Tiii.) From loDfi-
tudinal Hceioo of cFsophiuius of > 27-nuii. pig, abowing becinniDg dangatioiu of moeoebyme <m) for
miuoularis mucosie (mm): Ic, ooanw myofibriU« and, ff, finer fibrilla in circuUr l>y«ri vl, varicon myo-
fibrillii Id loDgitudinaJ Uyer.

these irregular, longitudinal rows of granules, instead of the fine-
meshed protoplasmic reticulum." "However, at the margins of
the cell, in the protoplasmic processes connecting it with neigh-
boring cells and also around the nucleus and between the myo-
fibrilliB, more or less ordinary granular protoplasm remains."
These granular fibrillre represent the rudiments of the myofibrillfe

462 HUMAN EMBRYOLOGY.

and occasionally branch and anastomose with each other. The
granular myofibrillae enlarge at certain points, usually near the
nuclei; here the granules become coarser, are closely packed to-
gether, and form spindle-shaped structures which taper off at each
end into myofibrillaB composed of a single row of granules. *'In
some cases the end of the spindle appears to break up into several
branches of fine granular fibrilte, which may anastomose with
neighboring fibrillae. ' ' * * For the most part, however, the spindles
are joined by the intermediate fibrillae into long varicose fibrils
which pass through several cells, extending parallel to the
elongated nuclei." ''The granular stage of the myofibrillae does
not persist long, however," as soon condensation and fusion of
the granules both in the spindles and in the anastomosing fibrillae
produce apparently solid varicose smooth fibrillae. These smooth
varicose fibrillae may be of great length, extending half-way around
the oesophagus, for example, and passing through several cells
or nuclear territories. **Soon there may be several running
through each cell, causing a marked longitudinal striation. " ' ' Be-
tween the spindles, the fibrillae are at first slender, but they
gradually become thicker, so that the fibrillae become of a uniform,
coarse caliber" (Fig. 328). ''Here and there finer fibrillae do
occur, but they are usually granular in structure and are probably
merely stages in the formation of the coarse smooth myofibrillae. "

"In later embryos the granular myofibrillae and spindles are
absent or inconspicuous, though smooth, varicose myofibrillae are
not infrequent. " "In the late fetus or adult the coarse myofibrillae
are sometimes few in number or altogether absent." The fine
myofibrillae, to all appearances homogeneous, are always present.

In the second period of the formation of smooth muscle from
the embryonal connective tissue the development of the myo-
fibrillae in this embrvonal connective tissue seems to follow a
different course from that observed in the younger embryos. The
presence of the large number of collagenous fibres makes the
process difficult to follow. "The fine myofibrillae appear to arise
directly as such, without passing through a granular stage," and
the coarse myofibrillae arise by increase in the caliber or by fusion
of several of the fine myofibrillae into a compact bundle. These
coarse myofibrillae differ from those seen in the earlier stages;
they are even larger in caliber and present no spindles or vari-
cosities, but in favorable preparations are seen in places to fray
out at the ends into fine homogeneous fibrillae indicating that they
are merely bundles of fine myofibrillae. In the late fetus and in
adult life there is usually a decrease in the number of coarse
fibrillae, with a corresponding increase in the number of fine myo-
fibrillae, probably from the splitting of the coarse fibrillae. And
"where there are few or no coarse myofibrillae, and at the same

DEVELOPMENT OP THE MUSCULAR SYSTEM. 463

time a rapid increase in the number of fine myofibrilltt," it would
seem that the latter increase by longitudinal division. In the later
stages, then, the fine myofibrillie appear while the coarse fibrillie
decrease in number. The fine myofibrillie arise by splitting of
the coarse fibrilla or in later stages by new formation in the
protoplasm. They become uniformly scattered through the proto-
plasm, while the coarse fibrilUe come to lie in more or less compact

Fid. 32fl.— (After McGill: Inter. Honat. f. Anmt. u. Phyg., Z4 Fig. 15, Tat. x.) From drcular
miucle layer of lower cPKiphagua of b lO-cm, pig embryo, ahoning per^isleoce of Hyacytium. elaetic librea
(el}, embryoDal connMIlve-tiMU* Mil (el), witJi collagencnu Ebrille iefj, protoplMinic bridges (pft), fine
myofibrillc (If), coarse myofibrillie ijc).

bundles, often near the surface. In later stages myofibrillie cease
to develop as new structures, but increase through longitudinal
splitting of the fibrillie already present.

At a certain stage in development collagenous fibrillie begin
to form throughout the mesenehjine and also in the smooth-muscle
syncytium, and in a single cell both myofibrillje. and collagenous
fibrillie frequently diflferentiate side by side (Fig. 329). The pres-
ence of collagenous fibrillae in the later stages of the smooth muscle
indicates the origin at this time of muscle from the embryonal
connective- tissue sjTicytium in which these fibrilte have already

464 HUMAN EMBRYOLOGY.

developed. This intimate relation of the collagenoas fibrillse with
smooth muscle may continue even in adult muscle and the col-
lagenous fibrillffi often run from the protoplasm of one muscle-
cell into neighboring cells, thus binding the tissue firmly together.

' ' In development, protoplasmic connections between the
muscle-cells and the connective-tissue cells are easily demonstra-
ted." Through the connecting bandsof protoplasm, myofibrilliemay
enter "the protoplasm of the connective-tissue cells or collagenous
fibrillse make their way into the muscle-cells." "In later develop-
ment, most of the collagenous fibrillas are crowded out of the
protoplasm of the muscle-cells into the intercellular spaces."

In the walls of the large blood-vessels elastic fibres may arise
in the margins of the muscle-cells and are only with difificulty
distinguished from the coarse myofibrillje.

« fioa fibrillc Uf). c
bnish 01 lioe myoiiDniiK (or), cxHia«tive-lis>ue coll (d>,

"In the region of muscle formation some of the embryonal
connective-tissue cells do not elongate or form myofibrillfe, but
persist as the interstitial connective-tissue cells. The connective
tissue, therefore, does not invade the muscle from without, but
arises in situ."

"After the layers of smooth muscle are established, the tissue
increases in amount in two ways: first, by a continuation of the
process of transformation of mesenchyme (or later of embryonal
connective tissue) into smooth muscle at the surface of the muscle
layer, or from the transformation of the interstitial cells. This
process predominates in earlier embryos. Second, the nuclei of
the already formed smooth muscle multiply by mitosis, especially
in more advanced fetal stages."

Cross-striated Muscle. — In the mammals and man all the
cross-striated muscle arises from the mesoderm, either directly

DEVELOPMENT OP THE MUSCULAR SYSTEM. 465

from the mesoderm or its mesenchyinal derivatives, as in the
head, or indirectly from the primitive segments, as with the deep
muscles of the back and the thoraco-abdominal musculature.

The main problem of its histogenesis has been to determine
if the adult multinucleated muscle-cell arises from a single cell
whose nucleus divides many times or from the fusion of several
cells. Each view has had many supporters since the time of
Schwann, who held the view of end-to-end fusion, and even to-day
the problem is unsettled. Bardeen (1900), in his studies on the
pig embryo, takes the view that each muscle-cell arises from a
single myoblast which elongates and the nuclei increase within
it by direct division. Godlewski (1902), working on the rabbit
embrj'o, found that several myoblasts fuse to form an adult fibre
and only rarely do the myoblasts remain single even in the
mvotomes.

FiQ. 330.— (Afi« Godlewski: Arch.
iDuiele liiyer q[ s 12-dAy csbbit embryo.
Many of the elemenU are bouod logelher

In the myotomes, muscle differentiation progresses from the
anterior to the posterior end of the myotome series. At first the
long axes of the myoblasts are at right angles to the sagittal
plane of the body, but as these epithelial cells of the myotome
differentiate into spindle-shaped myoblasts, their long axes be-
come parallel to the long axes of the body. The pointed ends
of the myoblasts, according to Godlewski (1902), push in between
other cells and anastomose to form a syncytium, and only rarely
are single cells found extending the full length of the myotome
with only one nucleus (Fig. 330). In this syncytium differentiation
proceeds and most muscle-fibres arise from several cells which
have thus fused into the syncytium. Cell division goes on in the
syncytium, the daughter cells retaining often protoplasmic con-
nections. The syncytium may extend from one myotome to another.
Thus, according to the view of Godlewski, cross-striated muscle
like the smooth muscle forms a syncytium, and distinct and
separate cells or fibres rarely are to be found.

This \'iew is somewhat different from that of Maurer, who
found that cell borders at certain stages become invisible, and

Vol. I.— 30

466 HUMAN EMBRYOLOGY.

concluded that the nuclei divided without cell division. Godlewski
holds that cell division goes on hand in hand with nuclear division
in the earliest stages of muscle formation, the cells retaining
protoplasmic continuity.

The muscle-forming cells are at first cylindrical and epithelial-
like. As the myoblasts increase in size they are found to contain
many small round granules scattered throughout the cell (Fig.
330). These granules soon become arranged in rows, first in the
central part of the protoplasm. They then migrate peripheral-
wards (Godlewski), forming the rudimentary fibrillae. As the
fibrillae develop the granules lie closer and closer together by in-
creasing in number, rather than size, until finally a continuous
thread is formed. Here again is seen a striking similarity between
the smooth and cross-striated muscle development in the formation
of the fibrill®. Wliether these granules actually fuse or are only
pressed together Godlewski could not determine. The granular
chains, as well as the continuous fibrillse which arise from them,
in later stages pass through several cell territories, and as the
fibrillae rapidly increase in length they soon extend the entire
length of a myotome. The granules between the fibrillae become
rarer and rarer as the fibrillse increase in number.

The fibrillae become arranged more and more parallel to the
axis of the cells and are grouped about the nuclei. The fibrillae
extend through several cells from one myotome septum to another.
The rich connections between the cells often make the myotome
one complete syncytial mass. The fibrillae are gathered together
into columns, which become spear or spindle shaped towards the
myosepta, and often fuse with the colunms in the next myotome
through the protoplasmic bridges connecting the myotomes (Fig.
331). The club-like ends of the fibrillae columns are often seen
to be composed of many fine fibrillae (Fig. 331). In later stages
some of the columns may pass through several myosepta, in-
dependent of cell or myotome boundaries ; many of them, however,
end at the myosepta in club-like thickening, often with tufts of
fine fibrillae, the primitive fibre components.

The simple fibrillae soon begin to show a segmentation into
two differently staining substances. Do the segments correspond
with the original granules which may not have completely fused
into the thread, or are they entirely new structures f The deeply
staining segment corresponds with the Q anisotropic band of the
adult fibre and the other with the I isotropic striation. Wagner,
Bardeen, and others have also observed that the fibrillae at first
show no cross-striation.

The histogenetic process during this first period is essentially
the same in muscles which arise independently of the myotomes.
This new formation of muscle from the mesoderm Godlewski found

DEVELOPMENT OF THE MUSCULAE SYSTEM. 467

was best observed on the surface of developing muscles. The
mesodermal cells elongate into spindle-shaped myoblasts, rich in
protoplasm and containing many granules. The myoblasts arrange
themselves with their long axes parallel and unite into a syncytium
by their processes. The nuclei divide by mitosis, but the daughter
cells often remain connected together. The fibrillte form in a
similar manner as described above in the myotomes.

The second period begins with the physiological degeneration
which has been described by S. Mayer (1886), Barfurth (1887),
Bataillon(1891, 1892), Schaffer(1893), Bardeen(1900), Godlewski
(1902). This account is based on the description of Godlewski

I.) la the inU
mbryo.

(1902). In certain regions of the developing muscles the fibrillar
columns are seen to break up and disappear, the nuclei become
irregular, and the direction of the long axis, which imtil now has
been parallel to the long axis of the fibre, is altered so that the
nuclei are often diagonal or crosswise. The protoplasm becpmes
more homogeneous and gathers about the nuclei in stellate masses'.
The nuclei become pale and poor in chromatin, but often retain
the power of division for a long time. In some forms of degenera-
tion the muscle-cells become vacuolated (Fig. 332). Many of the
degenerating muscle-fibres disappear. After the stage of de-
generation new muscle-fibres are formed by longitudinal splitting
of the normal ones already present.

The fibrillse multiply by longitudinal splitting and becomfe
grouped into the columns in such a manner that similar cross-

468 HUMAN EMBRYOLOGY.

etriations (Q and I) in the same muscle-fibre lie in the same
planes. Parallel with this process new striations appear, first the
Z and later the M zones. In a ten-weeks hiunan embryo the cross-
striation is already completely developed.

Both Bardeen and Godlewski noticed in early stages that
during mitosis the protoplasmic granules increase in number. At
this time the cell bodies usually split during mitosis, but occa-
sionally more than one nucleus is found in a cell. In later stages

a a

Fia. 332.— (After Godleiralii: Arch. t. mikr. AnBt., Bd. flO. Tal. vi, Fig. 10.) Giunw-pis imbrya

12.mm. long. Bc^nning of the deecaeiscian procesa. a, lone of & miude rudiment in which deseocm-
tion baa Dot begun; b, fibrils in which the continuity in appuvotly deatroycd; c, nusld in altered prni-

amitotic division occurs, and fibres come to have many nuclei, both
medial and peripheral. Godlewski believes that the fibrillte play
an active part in the wandering of the nuclei to the periphery.
The inner nuclei are present in the earliest phases of development
and later wander to the periphery of the musele-fibre. Mitosis
occurs in both inner and outer nuclei.

During the development of the myotomie muscles new myo-
blasts seem only to arise through division of the myoblasts already
present in the myotomes, and there is probably no direct trans-
formation of mesenchyme cells into myoblasts. But with those

DEVELOPMENT OF THE MUSCULAR SYSTEM. 469

muscles arising directly from the mesenchyme there is for a period
a continuous transformation of mesenchyme cells into myoblasts,
as in the muscles of the limbs and head. This process early
ceases, and new muscle-fibres then arise only by cleavage of those
present.

According to MacCallum (1898), who counted the fibres of
the sartorius muscle in man at various ages, muscle-fibres cease
to multiply in fetuses from 130 to 170 mm. in length, and hence-
forth the muscles increase in size by enlargement of the individual
fibres. Meek (1898, 1899) observed in several mammals (rat, cat,
and sheep) that the fibres decrease in number soon after birth.
The luck}^ fibres get into better relations with the nutritive supply,
etc., while the unfortunate ones are squeezed out and so degenerate
(a survival of the fittest). The increase in the size of the muscle
after birth is dependent on increase in the size of the individual
fibres. Morpurgo (1898) was unable to find this decrease in the
number of the fibres, but did observe that multiplication ceases
a short time after birth and muscles increased in size by increase
in the size of the fibres.

THE SEGMENTATION OF THE MESODERM.

The development of the voluntary skeletal musculature may
be said to begin with the segmentation of the dorsal division of
the tnmk mesoderm into the primitive segments. The musculature
arising from the primitive segments is both phylogenetically and
ontogenetically the oldest in the body.

It is uncertain which segment is the first one to form, Keibel
claiming that in mammals, and Maurer that in all vertebrates, the
most anterior one is the first to become segmented off from the
mesoderm. Paterson (1907) has shown, by experiments on chick
embryos, that the first segment to form is the most anterior one
and that segmentation progresses posteriorly. This probably holds
true for all vertebrates.

The segmentation of the mesoderm begins in embryos be-
tween 1.17 mm. (Frassi) and 1.38 mm. (Kroemer-Pfannenstiel)
in length. In the latter embryo there are 5 or 6 pairs of primitive
segments and in the former none. There is perhaps some varia-
tion in the time of the first appearance of the segments, for in
an embryo 1.54 mm. in length (Spec, Gle) there are no primitive
segments, while in an embryo 1.6 mm. in length (Unger-Keibel)
there are about 9 pairs. In an embryo of 2 mm. in length (Mall,
391) there are 8 to 9 pairs of primitive segments which are still
connected with the lateral mesoderm. Segmentation progresses
rapidly in a caudal direction. In embryos 2 to 3 mm. in length
the number of segments ranges from about 10 to 20 pairs; in

470 HUMAN EMBRYOLOGY.

embryos 3 to 4 mm. in length, from 20 to 30 pairs; 4 to 5 mm.,
30 to 35 pairs; 5 to 6 or 7 mm., 35 to 40 pairs. From 38 to 40
pairs of segments are formed, 3 to 5 occipital, 8 cervical, 12
thoracic, 5 lumbar, 5 sacral, and about 5 coccygeal. In embryos
of 7 to 9 mm. in length this segmentation attains its highest
development (Figs. 367, 336, 368, 335, 334). The segments soon
lose their individual identity as such, and in embryos from 10.5
to 12 mm. in length the myotomes fuse to form a continuous
column (Fig. 337). This fusion progresses in an anteroposterior
direction.

THK DIPFERENTHTION OF THE PRIMITIVE SEGMENTS.

Just as there is a progressive segmentation of the mesoderm
in an anteroposterior direction, so we find there is a progressive
differentiation of these primitive segments in the same direction.
Thus, in erabrj'os of 4 to 5 mm. in length the anterior segments
show quite advanced differentiation while the posterior ones still
retain the more primitive conditions.

Flo. 333.— (After y. I«nho«ek, Arch, f. Anat. u. Mij-mol.. 1881.1 CrofiB.wc[ioii

The differentiation of each segment follows a common plan
progressing in a cranio-caudal and a dorso-ventral direction. The
primitive segment is at first cubical, with simple epithelial walls
surrounding an empty cavity or myocoel. In sections the dorsal,
lateral, medial, and ventral walls are more or less clearly to be
recognized (Fig. 333). The first change which takes place is the
migration of cells from the walls into the ca\ity, especially from
the medial and ventrnl walls. Later, as the myocoel becomes filled

DEVELOPMENT OP THE MUSCULAR SYSTEM. 471

with these cells, this nidimeat, with much of the medial and ventral
walls, migrates medially towards the chorda and neural tube,
forming the rudiment of the sclerotome. Following the migration
of the sclerotome the dorsal wall grows ventrally along the medial
surface of the outer lamella to form the medial lamella of what
has now become the myotome. With the growth of this medial
lamella to the ventral edge of the outer lamella, with which it
imites, the myoccel becomes reduced to a narrow cleft between
the two lamella?. The myotome now consists of a two-layered
quadrilateral body, with the lateral or cutis plate, the medial or
muscle plate, dorsal and ventral edges, and anterior and posterior
edges which are in contact with the preceding and succeeding
myotomes (Fig. 334). In a three-
weeks embryo this condition is found
in the anterior segments while the
more posterior ones still show the first
stages of the primitive segments.

In an embryo 4.9 mm. in lengtli,
for example (Ingalls, 1907 ) , the
second coccygeal myotome is just
separating from the caudal mesoderm.
In the anterior coccygeal myotome the
myocopl is filled with sclerotome cells
arising from its walls. In the sacral
region these cells, together with tlie
medial and ventral walls, are pushing
towards the chorda and neural tube,
while in the anterior sacral region the

cranial part of the medial wall is F10.334.— (Afternnnirniamii^wiB)
broken through and it together with ^i^^ ^1';'?^ Z™dc'"?o't™«'"'"'
the sclerotome cells of the myocoel are

migrating towards the chorda and neural tube. In the lumbar
region the medial and ventral walls, together with the myoctel cells,
have migrated toward the chorda and neural tube, leaving a wide
opening into the myoccel, the intervertebral cleft. At the dorsal
edge of the mj-otome the inner lamella {muscle-plate) is beginning
to grow ventralwards along the medial surface of the outer lamella.
In the thoracic region this inner lamella has grown well towards
the ventral edge of the outer lamella, which edge has rolled
medially, and from this free edge sclerotome cells are still migrat-
ing. With the ventral growth of the inner lamella and its union
with the edges of the outer lamella, the opening into the myocrel
is gradually reduced in size, but persists towards the caudal end
of the ventral border as the intervertebral cleft. In this region
later lie the spinal nerves and segmental blood-vessels. The outer
lamella during this process has extended further ventrally and

472 HUMAN EMBRYOLOGY.

also increased in thickness, its cylindrical epithelial cells remain-
ing for the most part with their long axis at right angles to the
cleft-like myoccel. The medial lamella as it grows ventrally in-
creases in thickness; its cells become spindle shaped, with their
long axis parallel to the dorsal edge of the myotome. The cells
of the dorsal edge, however, retain longer their primitive epithelial
character and form the vegetative centre for the dorsal extension
of the myotome. In the anterior thoracic region cells from the
medial surface of lateral lamella separate from it to join the
medial or muscle-plate. The ventral edge of the myotome is
formed by the bending medially of the ventral edge of the lateral
plate, which has elongated ventrally during the formation of the
myotome. Ingalls also finds in this 4.9-mm. embryo that in both
sacral and lumbar regions the ventral edge is not very sharply
marked off from the surrounding mesenchyme. In the lumbar
region cells appear to be migrating from the edge of the myo-
tome into the limb bud. In the cervical region the migration
of cells into the arm bud is even more marked, and from some
of the myotomes distinct epithelial buds project towards the arm
bud from the lateral lamella near its ventral border. The fourth,
fifth, and sixth cervical myotomes also show migrating cells from
their ventral edges.

The cells of the medial or muscle lamella are gradually trans-
formed into elongated spindle cells extending in an anteroposterior
direction from one end of the myotome to the other. These cells
later form muscle-cells.

The fate of the lateral or cutis lamella is still in dispute, even
in the lower vertebrates. Most observers agree that the lateral
or cutis lamella gives rise to both muscle and connective-tissue
forming cells (Kollmann, Kastner, Fischel). Ingalls found muscle-
forming cells, but could not determine in the 4.9-mm. embryo
studied by him whether the lateral lamella gives rise to connective-
tissue cells or not. Bardeen (1900), in his studies on both pig
and man, concluded that the lateral lamella, except for the de-
generation of some of its cells, gives rise only to muscle-cells.

The ventral edge or portion of the myotome gives rise to the
ventrolateral trunk and neck musculature. The median or muscle
lamella is entirely transformed into muscle-fibres. By longitudinal
fusion and splitting of the myotomes arise the deep back muscles
of the trunk and neck. The deepest layers, however, probably
retain more or less of the primitive segmental arrangement
(Bardeen).

DEVELOPMENT OF THE MUSCULAB SYSTEM. 473

THE MUSCLES OF THE TRUNK.

The intrinsic muscles of the trunk are derived directly from
the myotomes. By the intrinsic muscles I mean, first, the deep
muscles of the back, — namely, those beneath the musculi serratus
posterior superior and inferior. In the adult the deep muscles,
especially in the lumbar and thoracic regions, are encased in the
fascia lumhodorsalis. Thus, the muscles from the trunk to the
shoulder-gii-dle are excluded from this group, and, as will be
shown below, probably do
not come from the myo-
tomes. The second group
includes the ventrolateral
muscles of the thorax and
abdomen,— namely, the Mm.
serratus posterior superior
and inferior, intercostales,
obliquus abdominis internus
and externus, rectus and
transversus abdominis, and
quadratus lumhorum. In
tiie third group are the pre-
vertebral muscles, the Mm.
longus capitis and colli, and
rectus capitis anterior. ,

The Deep Muscles of the
Back. — The deep muscles of
the back arise from the myo-
tome column which results
from the fusion of the myo-
tomes and the disappearance
of the myosepta. This

fusion, as we have seen, pro- F10.335.— (AttcrB^rcleemmdl^wiB.) Fn>mB-mm.

_, , embryo, »homng; elevfnth and twslflh thorarii: myo-

gresses m an anteroposte- ,om« «tendm« into body v^n wi.h the rib«.
rior direction, and already

in a 9-mm. embryo traces of segmentation, at least superficially,
are beginning to disappear in the cervical and thoracic regions
(Figs. 335, 336). This process is complete in embryos of 11 to
12 mm. in length (Fig. 337). The occipital myotonies, at least
the caudal ones, are probably fused into this myotome column
(Figs. 367, 368). Superficially all traces of segmentation are lost,
but the deeper portion of the myotomes lying in contact with the
vertebral column probably retains in man the primitive segmen-
tation, as described by Bardeen (1900), in the pig. Thus, the Mm.
interspinales, rotatores breves, levatores costarum, and intertrans-

474 HUMAN EMBRYOLOGY.

versarii probably retain throughout intra-uterine and extra-uterine
life the primitive segmental arrangement of the myotomes.

By longitudinal and tangential splitting of the myotome column
the various muscles of the back arise, and the subsequent seg-
mentation of muscles arising from the myotome column is a
seeondari' one and need bear no relation to the primitive seg-
mentation. This process of splitting has already began in an

Fhi. 3:ti>.— lAIter Bonteea find I.eRii.) Fnim Sjnm. cmbryn. slioning m}-oUilucii irith veulrml
exteiiMon iulu body mil arul premuncle muHS of llie uno ngion. Tlie pmiiu>rlt ihtatli liu ben cut
sway frum dl<ul part of tbe snii.

embryo 11 ram. in lengtli in tiie cervical and thoracic regions,
even wlnle traces of segmentation are still visible at the caudal
end of the myotome column (Fig. 337).

Tbe superficial portion of the myotome column seems at first
to split longitudinally into two main di\nsions, — a dorsal one which
gives rise to the spinalis and longissimus groups, and a ventro-
lateral one which gives rise to the iliocostalis group of muscles
(Fig. 337). In the cenical region this process is more complex
than in tlie thoracic region, while in the lumbar region the more
primitive conditions of the myotome column persist to adult life.

DEVELOPMENT OF THE MUSCULAR SYSTEM. 475

The details in the development of the deep back muscles
have never been studied. I have observed that in a 14-mm.
embryo practically all the deep muscles of the back are to be
recognized without great difficulty except the suboccipital muscles.
At this stage the Mm. rectus capitis posterior minor and major
and the obliquus capitis inferior form a more or less continuous
sheet. Through the different attachments of various portions of
this muscle sheet one can recognize the position of the individual
muscles. In a 20-mm. embryo these muscles are distinct and
easily recognized.

The development of the fascia lumbodorsalis proceeds parallel
with the development of the myotome column and its muscle
derivatives. In an 11-mm. embryo this fascia is already present
in the upper thoracic and lower cervical regions, enclosing the
muscles in a distinct sheath which extends from the spinous proc-
esses into the lateral region of the neck and thorax. This fascia
remains an important landmark between the true myotome muscles
and those which subsequently migrate into the more superficial
region, such as the Mm. trapezius, rhomboideus, and latissimus
dorsi, and in part also the Mm. serratus posterior superior and
inferior.

The growth of the dorsal muscles towards the mid-dorsal line
is dependent on the extension and formation of the vertebral
arches.

The Thoraco-Abdominal Muscles. — The thoraco-abdominal
muscles arise through the ventral extension of the thoracic myo-
tomes into the body wall. The myotomes begin to grow into the
body wall with the development and extension of the ribs. Even
in a 7-mm. embryo, before the myotomes are fused into a con-
tinuous column, this process has already begun (Fig. 367). In a
9-mm. embryo the myotome processes extend farther ventrally
than do the ribs (Figs. 335, 336). As the myotomes extend into
the body wall, they lie partially between the ribs and partially
lateral to them, where they fuse into a continuous lateral sheet
which extends beyond the tips of the ribs, ending ventrally in a
continuous column, the rectus rudiment, formed by the fusion
of the entire thickness of the myotome processes (Fig. 336). The
myotome processes also fuse over the medial surface of the ribs
to form a continuous medial sheet, which is continuous with this
rectus rudiment lying ventral to the tips of the ribs. The ribs
and this ventrolateral musculature gradually grow farther and
farther into the body wall and finally reach the mid-ventral region.
Meanwhile, long before this occurs, while the ventral edge of this
invading skeletal and musculature wall occupies the extreme
lateral position along the sides of the embryo, the muscles begin
to differentiate (Figs. 337, 347). Through longitudinal splitting

476 HUMAN EMBRYOLOGY.

off of the muscle column formed by the fusion of the ventral ends
of the myotome processes arises the M. rectus abdominis. Through
tangential splitting of the lateral sheet arises the M. obliquus
abdominis externus and more dorsal to this the Mm. serratus
posterior superior and inferior. The medial sheet gives rise to
the Mm. obliqnus abdominis intemus and transversus abdominis.
The portions of the myotome processes remaining between the

Fio. 337. — (After Birdeeu and Levia.) From ui ll-nua. embryo.

ribs give rise to the Mm. intereostales extemi and interni. They
are already clearly differentiated in an 11-mm. embryo. The Mm.
intereostales apparently always retain the primitive segmentation
of the rayotoraes. The lines transversa; of the rectus are often
spoken of as representing the primitive myosepta and the muscle
bellies between as primitive myotome segments. In the fusion of
the ventral ends of the myotomes to form the rectus, I have been
imable in early stages to recognize the myosepta, and it may be
that the segmentation of the rectus is a secondary process. The
segmentation of the M. obliquus abdominis extemus is for the

DEVELOPMENT OF THE MUSCULAR SYSTEM. 477

most part secondary, except as pointed out by Bardeen (1900),
traces of segmentation remain where it lies in direct contact with
the intercostales extemi throughout its period of development.
The Mm. obliquus abdominis intemus and transversus abdominis
do not retain any traces of the primitive segmentation.

Fia. 33S. — <AfUr Bacdeen tad Lewi.

In 14-mm. and 16-mm. {Fig. 349) embryos the abdominal
muscles are clearly differentiated and present much the adult
form, although they still occupy a more lateral position, and even
in a 20-mm. embrvo the two recti are widelv separated (Figs. 338,
339, 348).

478 HUMAN EMBRYOLOGY.

There are no observations that 1 am aware of that explain
the origin of the Unese semicircularis (Douglasi).

The Suhvertebral Muscles. — The subvertebral muscles of the
cervical regiou are formed by the growth of the myotomes on to
the ventral surfaces of the vertebral bodies and subsequent fusion
of these myotome processes into a continuous colunm to form
the Mm. longus colli and capitis. The M. iliopsoas is not derived
in this manner, but extends upwards from the femoral region
and belongs to the nmsculature of the leg.

THE MUSCLES OF THE PERINEUM.
Popowsky (1899) has given the best account of the develop-
ment of the muscles of the perineum. They arise from the mus-
culus sphincter cloaca?, a skin muscle which is present in a 2-months
embryo (Fig. 340). During the third month of fetal life it
divides into a M. sphincter ani extemus and a M. sphincter sinus
urogenitalis (Fig. 341). This division is dependent upon the
separation of the simple single cloaca! opening into two openings.
The M. sphincter ani extemus alters very little during the later

DEVELOPMENT OF THE MUSCULAR SYSTEM. 479

development, bat the M. sphincter urogenitalis undergoes many-
changes, giving rise as it does to perineal muscles. During the

P-W^AiflderttoKBt

v^«;>wfcndui

(Atter Popov
i,Fi«.l.> E

-iky.Anst.Hefle.fid.

iasmum-jniuia

^lisd

Kjouleiuki

iKbrani uUri"«

-<Afl*r Popo
ii. Fig. 2.)

W8ky. AQ.t. HellF. B.
Embryo 0( 3 monlhu.

ilbo<aytni<]iax
'.dorudis pails.

t spkmkram aianas

I pudtndus.
Hsp^iinderia

tr Popowsky, Anal. Heftf, B.I. '2

tH'adtio-
utrnasm

i. 345.— (After Pop

fourth to fifth month the M. sphincter urogenitalis gives rise first
to the M. ischiocavernosus, bulboeavemosus, and M. sphincter
urethra membranaceic (Figs. 342, 343, 344, 345). The M. trans-

480 HUMAN EMBRYOLOGY.

versus perinei are the last ones to develop out of the peripheral
and lateral part of the M. bulbocavemosus.

The M. levator ani arises from a quite different source and
only secondarily comes into relation with the M. sphincter ani
and the perineal muscles. The M. levator ani arises in connection
with the M. coccygeus and gradually descends to the rectum,
bladder, prostate, and vagina and thus comes into contact and
intimate union with the muscles of this region.

The difference in the nerve supply between the perineal
muscles and the M. levator ani indicates their different origin.

THE VENTROLATERAL MUSCLES OF THE NECK.

Under this heading are included three groups of muscles:
(1) the infrahyoid and diaphragm group, (2) the scaleni group,
and (3) the levator scapulae and serratus anterior. The Mm.
trapezius and stemocleidomastoideus arise in the occipital region
and migrate to the shoulder-girdle, and are described with the
muscles of the shoulder-girdle. The myotomes of the cervical region
do not appear to extend very far ventrolateralwards into the neck
region, as do the thoracic myotomes into the intercostal spaces
(Fig. 367). This ventral extension of the thoracic myotomes is
closely associated with the origin and development of the ribs.
In the cervical region the only apparent ventral extension of the
myotomes is between the transverse processes onto the ventral
surface of the vertebral column to form the rudiments for the
subvertebral muscles. There occurs, however, in the cervical re-
gion of very young embryos, 7 mm. in length, closely packed
mesenchyme or premuscle tissue in the region where later these
three groups of neck muscles differentiate. The origin of this
premuscle tissue is uncertain. It may arise entirely from the
mesoderm of this region or the myotomes may contribute cells
to it, but there is no direct proof of this nor of any distinct
myotome buds.

In a 9-mm. embryo the rudiments of the neck muscles are
beginning to differentiate. At this stage the infrahyoid premuscle
mass is especially well seen and apparently develops more rapidly
than the other groups (Fig. 367). In early stages the premuscle
tissue is continuous above with the tongue premuscle masses and
T)elow with the diaphragm masses. It consists of a distinct band
of premuscle tissue extending on either side, from the base of
the tongue, caudolaterally towards the tip of the first rib. It
forms the most ventral group of the neck muscles and already
is supplied by the ramus descendens nervus XII. Above the heart
towards the base of the tongue region the two lateral masses
approach each other and nearly meet in the midventral line;

n

DEVELOPMENT OF THE MUSCULAR SYSTEM. 481

as they descend, however, they become widely separated by the
heart and occupy a lateral position between the dorsolateral
angle of the heart and the vena cava superior. In later stages
as the heart descends into the thorax the muscle masses of the
two sides approach each other more and more, the approximation
extending from above downwards. In a 14-mm. embryo this ap-
proximation is nearly complete. At this stage the muscle mass
already shows cleavage into the Mm. stemohyoideus, stemo-
thyroideus, and omohyoideus ; the latter can now be traced to the
scapula. This cleavage process begins in embryos of about 11
mm. in length (Figs. 370, 379). In a 20-mm. embryo the muscles
have almost the adult form. The muscles of the two sides lie
parallel to each other near the midventral line extending from
the hyoid and thyroid cartilages to the rudimentary halves of the
sternum.

The diaphragm arises from two premuscle masses, one on
either side, which are, in a 9-mm. embryo, closely connected with
the caudal end of the infrahyoid masses and at this stage lie in
the lower cervical region, and, like the infrahyoid masses, there
is no direct proof of their origin from the third to the fifth myo-
tomes (Fig. 369). The diaphragm premuscle mass already ex-
tends a short distance into pleuroperitoneal septum, although still
some distance above the first rib. The plirenic nerve enters the
mass. In an 11-mm. embryo the diaphragm muscle mass has
descended some distance into the thoracic cavity, carrying with it
the nerve, and all connection with the infrahyoid muscle mass has
of course disappeared (Fig. 379). In a 14-mm. embryo the dia-
phragm and its muscle have descended still farther into the
thoracic cavity, to occupy more nearly the adult position, and the
muscle masses of the two sides have joined. The muscle is best
developed in the dorsal portion of the diaphragm in the region of
the vena cava inferior and the oesophagus. The crural attach-
ments to the vertebral column do not develop until later.

The scaleni muscles arise from premuscle tissue, ventral to
the lower cervical myotomes. From the material at my disposal
I have been unable, however, to trace satisfactorily the early
development. Already in an embryo 11 mm. in length three
scaleni muscles are fairly well differentiated, with the adult attach-
ments. They apparently develop in situ except for the caudal
extension of the M. scalenus posterior to the second rib.

The Mm. levator scapulae and serratus anterior, which arise
from the premuscle tissue of the lower cervical region and second-
arily migrate to the thoracic region, are described with the
muscles of the shoulder-girdle.

Vol. T.— 31

482 HUMAN EMBRYOLOGY.

THE MUSCULATURE OF THE EXTREMITIES.

The limb buds first appear, in embryos of about 4 mm. in
length, as oval projections from the lateral surface of the WolflSan
ridge. The arm bud lies opposite the ventral ends of the fifth
to eighth cervical and first thoracic segments, and the leg bud
opposite the first to fifth lumbar and first sacral segments. At
first the limb buds are filled with a closely packed mesenchyme
derived from tlie parietal layer of the mesoderm. As the limb
buds increase in size, the myotomes extend ventrally in such a
manner that the dorsal attachment of the limb bud lies over the
ventral portion of the myotomes.

One of the important and much-disputed questions concern-
ing the origin of the limb muscles is the part which the myotomes
play or do not play in their origin. It has often been assumed
that the myotomes send off large buds into the limbs which com-
bine in various ways to form the muscles, and that the brachial
and lumbosacral nerve plexuses were indicators of the complexity
of these combinations. Mall (1898) expressed this idea in describ-
ing the relations between nerve and muscle in the following sen-
tence: **As the segmental nerves appear, each is immediately
connected with its corresponding myotome, and all the muscles
arising from a myotome are always innervated by the branches
of the nerve which originally belonged to it.'' While this re-
mains true for the muscles which actually do come from the myo-
tomes directly, it does not apply to the muscles of the limbs.
There are no observations of distinct myotome buds extending
into the limbs, such as have been observed in the lower vertebrates
or such as can readily be seen extending into the thoracic wall.
A number of observers, however, have found in embryos 4.5 to
5 mm. in length a diffuse migration of cells into the limb buds
from the ventral and ventrolateral portions of the myotomes that
lie opposite the limb buds: Fischel (1895), Ingalls (1907), Kastner
(1890), and Kollmann (1891). Ingalls (1907) not only observed
this diffuse migration of cells from the ventral portion of the
myotomes into the limb buds in an embryo 4.9 mm. in length,
but also saw distinct processes from the lateral surface of the
myotome near its ventral edge extending lateralwards towards
the limb bud.

All observ^ers seem to agree, however, that these migrating
cells soon lose their epithelial character and become indistinguish-
able from the cells of the closely packed mesenchyme filling the
limb bud. Kollmann (1891) has pictured these cells from the
myotome as forming a continuous band, gradually extending be-
neath the ectoderm of the limb bud, first on the dorsal then on
the ventral side of the limb bud, and continuing on into the

DEVELOPMENT OF THE MUSCULAR SYSTEM. 483

ventrolateral body walL This myotome sheath he pictures as
lying between the ectoderm and the axial core of somewhat less
closely packed mesenchyme. At the distal end of the limb bud thi^
axial core, according to Kollmann, pushes through the muscle band,
thus dividing it into a dorsal or extensor layer and a ventral or
flexor layer. KoUman's scheme, however, has not been verified
by more recent observers.

Bardeen (1907) and Lewis (1902) were unable to find either
myotome buds or distinct migrating cells from the myotomes
into the limb buds, and it is possible that the myotomes play no
part whatever in the origin of the musculature of the limbs. The
character of the mesenchyme found in the early limb buds is very
similar to that in the branchial arches from which the head
muscles arise. The idea that myotomes play a role in the origin of
the muscles of the head must be abandoned, even by the most
ardent supporter of the segmentation theory. The limbs, phylo-
genetically and ontogenetically, are of later origin than the
branchial arches, and thus there is even less reason for assuming
that the limb muscles are derived from the myotomes than that
the branchial muscles have a similar origin. As the limbs are
of later origin than the trunk musculature, it is but natural to
expect the limb musculature to arise independently.

It has been impossible with our present methods for even
the strongest adherents of the myotomic origin of the limb muscles
to follow the complete history, inasmuch as the cells, if any such
are given off from the myotomes, mix with the mesenchyme cells
of the limb bud and soon become indistinguishable from them.
The description of the differentiation of the limb musculature
must begin then, whichever view we may take as to its source,
with the first appearance of the premuscle masses in embryos of
about 9 mm. in length. Considerable time has thus elapsed be-
tween the period when migrating cells have been observed enter-
ing the limb buds and the first stages of muscle differentiation.

In both arm and leg the proximal muscles are the first ones
to be recognized. There is a progressive proximodistal differ-
entiation, the hand and foot muscles being the last to differentiate.
The muscles of the arm differentiate slightly earlier than those of
the leg.

THE MUSCLES OF THE SHOULDER-GIRDLE AND THE ARM.

The Shoulder-girdle. — The muscles attached to the shoulder-
girdle and connecting it with the tnmk may be divided into several
groups: (a) the trapezius and stemocleidomastoideus which
descend from the occipital region; (b) the rhomboideus major
and minor, the levator scapulae, and the serratus anterior, which

484 HUMAN EMBRYOLOGY.

arise in the lower cervical region; (c) the subclavius and omo-
hyoideus; (d) muscles, arising from the arm bud, that spread
out from the arm and shoulder-girdle to the trunk, the latissimus
dorsi, and pectoralis major and minor.

(a) The common rudiment of the Mm. trapezius and stemo-
cleidomastoideus first appears in embryos of about 7 mm. in
length, and lies ventral to the two caudal occipital and two an-
terior cervical myotomes (Fig. 367). It stands, however, more
in relation to the branchial arch series than to the myotomic
muscles. There are no direct observations on the origin of the
cells composing this rudiment, but from its position and nerve
supply it may be best considered as the caudal member of the
branchial arch series. At this early stage it consists of closely
packed cells, indistinguishable from the surrounding mesenchyme
cells except for the greater condensation of the mass and the
presence of the nervus accessorius which runs for some distance
within the mass. The anterior end of the muscle mass lies close
to the place where the nervus accessorius leaves the vagus. From
this position there is a gradual extension caudalwards towards
the arm bud of the premuscle tissue, which in a 9-mm. embryo
reaches to about the level of the fourth cervical myotome (Fig.
368). At this stage its caudal end already shows signs of splitting
into two divisions for the Mm. sternocleidomastoideus and trape-
zius. In an 11-mm. embryo the two divisions are quite widely
separated caudally, the trapezial portion extending to about the
sixth cervical nerve and the sternomastoid portion to near the
rudimentary clavicle which at this stage lies far anterior to the
first rib (Figs. 337, 347, 367). The trapezius has not attached
itself to the shoulder-girdle. The trapezius is a thick columnar
mass extending from the occipital region caudalwards parallel
and close to the vagus nerve. It has extended only slightly towards
the spinous processes and is connected with them by a layer of
fascia. The thick deep cervical fascia separates it from the more
dorsal lying myotomic muscle masses. In a 16-mm. embryo the
entire arm and shoulder-girdle have migrated caudally. The Mm.
trapezius and sternomastoideus are now separate and distinct
throughout their entire lengths. The trapezius has gained its
attachment to the spine of the scapula and adjoining portion
of the clavicle (Fig. 349). It has also spread as far caudally
as the sixth rib and dorsally towards the spinous processes and
ligamentum nuchap. The anterior end of the muscle does not ex-
tend as yet to the occipital cartilage. Not until after the embryo
is over 20 mm. in length does the trapezius acquire its adult ex-
tent (Fig. 338). The splitting of the trapezius into the divisions
sometimes found in the adult is a secondary process and not to
be observed in the earlv embrvo.

DEVELOPMENT OF THE MUSCULAR SYSTEM. 485

The M. stemocleidomastoideus also shows marked advance
in a 14-mm, embryo, extending as it does from the mastoid process
and occipital region to the clavicle. It has already begun to split
into two divisions corresponding to the stemomastoid and cleido-
mastoid. The accessory motor-nerve supply from the cervical
region to the trapezius and stemocleidomastoideus is secondary
and does not indicate a myotomic origin for any portion of the
muscles.

(b) The exact origin of the tissue which gives rise to the
Mm. levator scapulas, serratus anterior, and rhomboidei is un-
certain. It has not been possible to trace them back to the myo-
tomes. In a 9-mm. embryo the levator scapulae and serratus an-
terior are beginning to differentiate from the mesenchjnne in the
region of the ventral ends of the lower cervical myotomes (Fig.
368). The premuscle mass forms at this ^tage a continuous
column, with no distinct attachments to the vertebrae or ribs over
which it extends for a short distance. In an 11-mm. embryo the
muscle mass for the levator scapulae and serratus anterior is well
defined, but still forms a column, oval in section, from the cervical
region to the thorax (Fig. 337). The thoracic portion, the future
serratus, becomes more and more slender towards the caudal
end and has distinct digitations to the upper nine ribs, that to
the ninth rib containing but a few fibres. Neither muscle has
attached itself to the scapula. The attachments to the cervical
vertebrae are present, however. The serratus now begins to change
into a broad, flat muscle and the lower digitations enlarge, and
in a 14-mm. embryo it begins to resemble the adult form (Fig.
349). At this stage the scapular attachment is present and evi-
dently plays a part in the change of form and extension of the
muscle (Figs. 338, 346).

The development of the Mm. rhomboideus major and minor
has not been followed. One can distinguish in a 14-mm. embryo
the common muscle mass between the dorsal border of the scapula
and the spinous processes. Owing to the relatively anterior posi-
tion of the shoulder-girdle at this stage, the rhomboid mass only
covers the uppermost portion of the M. serratus posterior superior.
In later stages, as the arm and shoulder-girdle migrate caudally
over the thorax, the rhomboidei come to overlap more and more
the serratus posterior until finally the adult condition is attained,
in which the caudal border of the M. rhomboideus major lies
caudal to that of the serratus post. sup.

(c) The M. subclavius apparently develops in situ from the
mesenchyme of the cervical region before the shoulder-girdle
migrates caudally. It is sharply defined in a 14-mm. embryo.
At this stage it has an anteroposterior direction, as the clavicle
is still some distance anterior to the first rib. As the rib grows

486 HUMAN EMBRYOLOGY.

towards the midventral line the costal attacbmeDt is carried
medially, and as this process is taking place the clavicle comes
to he closer to the first rib, and thus the subclavius muscle assumes
more and more a horizontal position.

The M. omobyoideus splits oflf from the infrahyoid muscle
mass and has already secured its attachment to the scapula in
a 14-mm. embryo.

U.glut.mtd. M.|lut.m

(d) The Mm. latissimus dorsi and teres major are closely
associated in their origin from the premuscle sheath of the arm,
the teres developing in situ while the latissimus gradually spreads
caudally over the side of the thorax. In an 11-mm. embryo it
extends to the fourth rib (Fib. 337), at 14 mm. to the eighth or
ninth, and at 16 mm. the attachment to the last three ribs is
attained, while dorsally the muscle is continuous with the lumbo-
dorsal fascia. Not until the embryo is over 20 mm. in length
do the muscle fibres extend to the crest of the ilium (Fig. 338),
The teres major is well developed in an embryo 14 mm. long.

DEVELOPMENT OF THE MUSCULAR SYSTEM. 487

The pectoral premusele mass from which both the Mm. pec-
toralis major and minor arise is clearly indicated in a 9-mm.
embryo. It lies in the lower cervical region on the medial side
of the arm bud. This premusele mass is widely continuous with
the arm premascle sheath and lies almost entirely anterior to the
first rib. In an 11-mm. embryo it reaches about the level of the

M. quailr*. fem . M. obi, int.

Fia. 347— (After BMileen and Uw».) Mnlian view o[ body nil and limba of sn ll-mm. embryo.

third rib, but the two muscles still form a single columnar mass
attached to the humerus, to the coracoid process, and to the
clavicular rudiment (Fig. 347). As the mass differentiates it flat-
tens out and extends eaudoventrally to the region of the distal
ends of the upper ribs. In a 14-mm. embryo the caudal end of
the muscle has extended near to the tip of the fifth rib and the
"muscle has begun to assume more the adult form, with fibres
arising from the upper five ribs and sternal anlage as well as
from the clavicle. At this stage the proximal portion of the muscle

488 HUMAN EMBRYOLOGY.

has split into the major and minor portions, the one attached by-
tendon to the humerus and the other to the coracoid process. Both
muscles fuse together near the costal attachments. In a 16-nMn.
embryo the two muscles are quite distinct, the pectoralis major
now extending to the sixth rib and showing a distinct cleavage
between the costal and clavicular portions (Figs. 339 and 349).
The pectoralis minor has now its distinct attachment to the second,
third, and fourth ribs.

The pectoralis major early splits into a series of overlapping
bundles, and during the migration of the muscle the superficial
fibres of each bundle move farther caudally than the deeper ones,
giving the overlapping condition found in the adult. The tendon
of insertion at first consists of a single sheet, but later from its
distal end the second deeper sheet gradually spreads proximally
and in an embryo of 40 mm. exceeds the superficial or ventral
one in breadth. The M. pectoralis major is carried towards the
midventral line with the growth of the ribs and sternal rudiments.

The Muscles of the Arm. — The remaining or intrinsic muscles
of the arm develop in situ and, as they differentiate from the
arm blastema, have approximately the same position that they
later occupy in the adult. In an embryo of 9 mm. in length the
skeletal core has already begun to differentiate as a thick rod
in the middle of the arm bud ending distally in the hand plate
(Fig. 336). On all sides, however, and at the distal end this
skeletal core gradually merges into the surrounding blastemal
sheath in which the muscles later appear, although the positions
of only the pectoral and latissimus premuscle masses are recog-
nizable at this stage. As the muscles differentiate their tendons
likewise form in situ, and the muscles are thus from the first in
connection with the skeletal structures by a condensed mesenchy-
mal blastema out of which the tendons later develop.

The Muscles of the Shoulder and Arm. — The Mm. deltoideus,
teres minor, supra- and infraspinatus arise from a common pre-
muscle mass continuous with the pectoral mass and the common
arm sheath (Fig. 336). In an 11-mm. embryo the M. deltoideus
has partially split-off from the mass towards its origin from the
acromion and clavicula (Fig. 337). In embryos of 14 to 16 mm.
in length it has much the adult form (Fig. 349), with usually a
distinct slip arising from the fascia over the M. infraspinatus.
In a 20-mm. embryo it has practically the adult form and attach-
ments (Figs. 338, 339, 346, 348). The development of the acromion
from the cephalic border of the scapula separates in part in an
11-mm. embryo the M. supraspinatus from the M. infraspinatus.
The M. supraspinatus lies at first on the medial surface of the
scapula (Fig. 347). Later it comes to lie along the cephalic border,
as in 16-mm. and 20-mm. embryos (Fig. 350, 351, 346), and only

DEVELOPMENT OF THE MUSCULAR SYSTEM. 489

in later stages, with the growth of the cephalic border, does the
muscle acquire its position on the lateral surface of the scapula.
The Mm. infraspinatus and teres minor are from the first very
closely associated and cover in an 11-mm. embryo only a portion
of the lateral surface of the scapula (Fig. 337). In a 14-mm.
embryo the muscle is quite distinct from the M. deltoideus, but
does not cover the whole of the fossa infraspinata even in a 16-mm.
or 20-mm. embryo (Figs. 349, 338, 346).

Fig. 348.— {After Binleen and Lewis.) Median viev of body w^l uid limbs of a SO-mni. pmbryo.

The M. suhscapularis is more or less isolated from the other
muscles from its first appearance, and occupies in an 11-mra.
embryo only a small portion of the median surface of the scapula,
and not until the embryo is more than 20 mm. in length does it
occupy the entire medial surface of the scapula (Figs. 350, 351).

The M. triceps brarhii arises along the posterior and lateral
surfaces of the humerus extending from the scapula to the ulna,
and even in an 11-mm. embryo indications of the three heads are
present, while in a 16-ram. embryo thev are verv distinct (Figs.
337, 338, 346, 349, 350, 351).

490 HUMAN EMBRYOLOGY.

The Mm. biceps brachii, coracobrachialis, and brachialis are
intimately fused together in very early stages and probably arise
from a common premuscle mass. The places of origin of the two
heads of the biceps at this early stage are close together, and
only by the later growth of the scapula do they become separated.
The three muscles are to be recognized in embryos of from 14 to

M.obl.ext. Cu^ulX'U.lut.doni
FlQ. 340.— (After Lewis.) Lateral view of arm of a lO-mm. embryn.

16 mm. in length, and the long tendon of the caput longum is
to be recognized in an embryo of 14 mm. The distal end of the
common muscle mass differentiates later than the proximal ( Figs,
338, 339, 346, 347, 348, 349. 350, 351).

The Extensor Muscles of the Forearm. — The extensors differ-
entiate somewhat earlier than the flexors (Figs. 337, 338, 339, 346,
349). The common extensor premuscle mass on the laterocephalic
side of the forearm first splits, in an embryo of about 11 mm. in
length, into three groups of muscles, of which the largest and

DEVELOPMENT OP THE MUSCULAR SYSTEM. 491

most superficial extends from tbe lateral condyle to the four ulnar
digits. It is a thin layer spreading over the ulnar two-thirds of
the foreann and distally joining the undifferentiated blastema of
the digits. On its radial side proximally it is intimately fused

in. M-subscsp.

with the second or radial group. From the superficial extensor
mass later differentiate the Mm. extensor digitorum communis,
extensor carpi ulnaris, and the extensor digiti quinti proprius.
(According to Grafenberg (1905), the ext. dig. V. prop, arises
in common with the deep extensor mass.) The separation of
the muscles of the superficial extensor mass begins in the carpal
region and extends proximally (Grafenberg) in the later stages

492 HUMAN EMBRYOLOGY.

as the tendons differentiate from the blastema of the digits.
The radial group extends from the epicondylus lateralis and
adjoining portion of the humerus distally along the radial and
adjoining extensor or dorsal surface of the forearm. It appears
to arise in situ along the radial surface, and not to have wandered
there from the extensor surface as claimed by Grafenberg (1905).
The mass early divides into two parts at the distal end, one, the
brachioradialis, fusing with the distal end of the radius, and the
other, the extensor carpi radialis longus and brevis, passing be-
neath the deep extensor mass to fuse with the blastema at the
proximal ends of the second and third digits. The deep extensor
mass lies beneath the radial portion of the superficial, becoming
itself superficial over the distal radial surface of the radius and
carpus and fusing with the blastema of the first and second digits.
At a later stage this mass divides into two groups, a radial one
for the Mm. abductor pollicis longus and extensor pollicis brevis,
and probably the supinator, and an ulnar division for the extensor
pollicis longus and extensor indicis proprius.

Not until the embryo is about 20 mm. in length does the com-
plete isolation process of the various extensor muscles reach an
end. The extensor digiti V. prop, is not split oflf until later.

The Flexor Muscles of the Forearm. — The development of
the flexors is more diflBcult to follow than the extensors, and, ow-
ing to the concave volar surface of the forearm and carpus, the
flexor muscle masses extend much farther distally than do the
extensors (Figs. 347, 348, 350, 351). In an 11-mm. embryo, how-
ever, one can distinguish a small superficial layer and a voluminous
deep layer. The superficial layer lies more on the radial side of
the volar surface and already shows indications of a radial mass
extending from the epicondylus internus to the blastema at the
distal end of the radius; later this mass splits into the Mm.
flexor carpi radialis and the pronator teres. The latter extends
farther distally on the radius in early stages, but, as the distal
part of the radius grows faster than the proximal, the distal
attachment of the pronator comes to lie farther and farther from
tlie distal end of the radius. The remaining portion of the
superficial layer develops into the M. palmaris longus. It is in-
timately fused with the proximal part of the radial mass, but
distally it extends on to the volar surface of the carpus, but with
the elongation of the skeleton of the forearm the muscular belly
comes to lie more and more over the proximal portion of the
forearm.

The deep flexor muscle mass is much more extensive and
thicker than the superficial, extending from the epicondylus in-
ternus over the entire volar surface of the forearm and carpus
into the blastema of the digits. Even in an 11-mm. embryo the

DEVELOPMENT OF THE MUSCULAR SYSTEM. 493

ulnar side already shows the beginning of the splitting oflf of the
M. flexor carpi ulnaris which reaches to the blastema of the os
pisiforme (Fig. 347). As the M. flexor carpi ulnaris increases in
size it spreads over the ulnar side of the deep flexor mass and
in an embryo 16 mm. in length is quite a distinct muscle.

The remainder of the deep flexor mass, even in an 11-mm.
embryo, shows indication of cleavage into a superficial flexor
digitorum sublimis and a deeper flexor digitorum profundus. The
mass extends from the epicondylus intemus and volar surface
of the forearm distally over the carpus without indications at
this stage of a longitudinal splitting over the carpal region. The
thick portion of the muscle in the carpal region has been designated
as a separate M. flexor digitorum brevis by Grafenberg, but it
appears to represent merely the distal part of the mass which
later recedes to the volar surface of the forearm as the latter
increases in length. The tendons of the two layers of the deep
flexor mass gradually differentiate from the blastema of the digits
and develop in situ as the digits increase in length. In an embryo
20 mm. in length the characteristic adult arrangement of the
tendons is attained, although the recession of the muscle bellies
on to the forearm is not complete nor the longitudinal splitting
which progresses in a distal proximal direction. At this stage the
M. flexor pollicis longus is easily recognized, although it is not
completely split off from the M. flexor digitorum profundus. The
Mm. lumbricales appear to differentiate in situ from the distal
portion of the deep flexor mass, and I have first been able to
recognize them in an embryo 16 mm. in length, but they probably
appear slightly before this stage.

The origin of the M. pronator quadratus is uncertain, and
I am not able to determine whether it splits off from the deep
flexor mass or arises independently. It is easily recognized in an
embryo of 16 mm. According to Grafenberg, it has a greater
proximal extent in early stages than in the adult.

The Intrinsic Muscles of the Hand. — The Mm. interossei ap-
pear to arise from a common volar muscle mass. In a 16-mm.
embryo the first signs of differentiation appear ; later the common
muscle mass splits into the various muscles which migrate from
the volar surface towards the dorsal surface of the hand between
the metacarpals.

The Mm. abductor dig. V. and flexor digiti V. arise from a
common muscle blastema, lying more on the ulnar side, and later
wander volarwards (Grafenberg). The M. opponens dig. V. dif-
ferentiates from the common interossei muscle mass (Grafenberg).

The thumb muscles develop from a common muscle mass, ex-
cept the M. adductor pollicis, which is always separated from the
others by the tendon of the M. flexor pollicis longus.

494 HUMAN EMBRYOLOGY.

THE MUSCLES OF THE LEG.

The muscles of the leg, like those of the arm, develop from
the premuscle sheath of condensed mesenchyme which surrounds
the axial skeletal rudiment. In embryos of about 11 mm. in length
this common muscle blastema begins in the proximal part of
the leg to differentiate into the muscles. According to Graf enberg
(1904), the nerves enter a common muscle mass for each group and
later this mass splits into the various muscles of the group.
Graf enberg 's description thus corresponds with that given for the
arm. Bardeon (1907), however, finds that the individual muscles
differentiate separately from the general muscle blastema, first as
small centres about their nerves, and from these centres the muscle
gradually extends towards origin and insertion. Whether this
extension is brought about by differentiation of the mesenchyme
into muscle or by active proliferation of cells of the original muscle
nucleus is not clear from Bardeen's account. If we assume, how-
ever, that in these early stages the mesenchyme continues to be
transformed into muscle about the original centre, Bardeen's ob-
servations come more into accord with the observations of Graf en-
berg and Lewis (1902). Bardeen's (1907) accoimt is here adopted
as a basis for the following section on the development of the
muscles of the leg.

The Femoral Group. — The femoral group, comprising the
Mm. iliopsoas, iliacus, pectineus, quadriceps femoris, and sar-
torius, arises from the muscle blastema on the ventral side of the
thigh and into it pass the N. femoralis and its branches.

The M. iliopsoas arises from that portion of the femoral
blastema which embraces the N. femoralis as it passes into the
limb bud. In subsequent development the M. iliacus spreads out
over the ilium and the M. psoas major extends upwards along
the roots of the femoral nerve to form its attachment to the
vertebral column (Fig. 355), and in close union the two muscles
extend distallv to be attached to the trochanter minor. The M.
psoas minor seems to split off from the M. psoas, but this is
uncertain.

The origin of the rudiment of the M. pectineus is uncertain,
but it probably arises either from the iliopsoas mass or the M.
adductor longus. In a 14-mm. embryo it is quite distinct, extend-
ing from the pubis to the femur (Fig. 354). A portion of the
muscle probably arises in connection with the M. obturator
extemus.

The rudiment of the M. quadriceps femoris first appears in
an embryo of about 11 mm. in length as a single mass lying over
the anterolateral aspect of the middle of the shaft of the femur
(Figs. 337, 347, 352, 353). In a slightly older embryo the mass

DEVELOPMENT OF THE MUSCULAR SYSTEM.

M. quulr. r«n. '
Flu. 35^.— lAttcr BantMD.J Mediui viav of pramuKi

Fici. 353.— (After B«nloeii.) 1^1

496 HUMAN EMBRYOLOGY.

begins to show definite differentiation into the four portions, the
Mm, rectus femoris, vastus lateralis, vastus intermedins, and vas-
tus medialis (Fig. 354). In a 20-mm. embryo the various muscles
of this group are all clearly demarcated and attached to the
skeletal apparatus by distinct tendons (Figs. 338, 346, 355).

The M. sartorius appears to arise from a distinct rudiment
proximal to that of the quadriceps mass (Fig. 353), and differen-
tiation gradually extends towards the ilium and tibia. The M.
sartorius is at first relatively larger than the quadriceps group,
but by the fourth month the quadriceps have overtaken it and at
birth it is only a little larger relatively than in the adult (Figs.
354, 355, 358, 357, 339, 348).

Fio. 3M.— (AfMr Bsrdeen.) Lateral view of the miudeg of the-thigh of > 11-nim. embo-o.

The Obturator Group. — The obturator group probably arises
from a common muscle mass Ij-ing along the anteromedial portion
of tlie femur (Figs. 347, 352), Cleavage is first apparent, in an
11-mra, embrj^o, in the proximal section of the region, into masses,
one for the obturator portion of the M, adductor magnus and
possibly also the M. obturator esternus, the other for the Mm.
adductor longus and brevis and tlie gracilis. In an embryo of
14 mm, the individual muscles may be clearly recognized, although
the tendons are not as yet well differentiated (Figs. 356, 359).
But by the time an embryo is 20 mm. in length the tendons of
origin and insertion are well differentiated to the skeletal attach-
ments {Figs. 348, 357, 358, 359, 360) and the obturator and sciatic
portions of the M. adductor magnus have fused.

The Gluteal Muscles. — According to Grafenberg, all the hip
musculature, including the Mm. glutieus maximus, medius, and
minimus, tensor fascia; latie,piriformis,obturator intemus, gemellus
superior and inferior, and quadratus femoris, arise from a cone-
shaped mass found at the distal end of the pelvis during the fifth

DEVELOPMENT OF THE MUSCULAR SYSTEM. 497

week. Bardeen deri\es these muscles from four mdiments which
first appear about the ends of their nerves.

The superior gluteal group consists of the Mm. glutteua
medius and minimus, piriformis, and tensor fasciae lata;, which
are intimately united in embryos 11 mm. in length (Figs. 337,
353). In a 14-mm. embryo the M. tensor fascia latffi has split
off from the lateral edge of the two gluteals. According to
Grafenberg, the M. tensor fascis latae is at first inserted into

Fio. 3S5.— (Aft«r Bardeen.) Latenl vie* of the musclee ot the thigh of ■ 20-mm. embryo.

the rudiment of the trochanter major, but after splitting off
from the gluteal it migrates laterally and loses its attach-
ments to the trochanter (Figs. 338, 346). At this stage the
M. piriformis is still closely fused with the gluteals, which
lie over the acetabulum, extending from the femoral margin of
the ilium to the rudiment of the trochanter major. The Mm.
gluta^us medius and minimus gradually extend over the surface
of the ala oss, ilium. Grafenberg finds that the M. piriformis is
from the first attached to the sacrum, but, according to Bardeen, it
is at first separate and only later extends to its sacral attachment.

Vol. I.— 32

498 HUMAN EMBRYOLOGY.

The rudiment of the M. glutteus maximus is separate from
that of the other gluteal muscles (Bardeeu) and slightly fused
with the rudiment of the short head of the biceps. At first it
only slightly overlaps the M. gluteus medius in the trochanteric
region, but it gradually extends over this muscle to the ilium,
sacrum, and coccyx, and becomes separated into two portions, one
being inserted into the femur and the other into the fascia latte.
In the embryo each portion has a separate nerve.

The M. quadratus femoris (Figs. 347, 352, 359, 360) seems to
arise early from a distinct rudiment tying between the anlage of
the tuber ischiadicum and the trochanter major, but close to the
rndiment for the Mm. obturator internus and gemelli on the ischial
Hide of the hip-joint (Bardeen). The Mm. obturator internus

}. 351).— lAfler Bardeei

and gemelli are at first closely united, but, as the obturator ex-
tends over the pelvic surface of the foramen obturatum from its
original attachment to the ischium, the two gemelli retain the
original attaciiment and are thus split off from the obturator. The
nerve of the M. obturator int. is carried into the pelvis with the
extension of the muscle.

The Posterior Thigh Muscles. — The hamstring muscles, in-
cluding the Mm. semiteudinosus, semimembranosus, biceps femoris,
and the sciatic portion of the M. adductor magnus, differentiate
from the muscle blastema on the dorsal (plantar) side of the
thigh (Figs. 347, 352). They are all distinctly differentiated in
a 14-mm. embryo (Fig. 356). The M. semimembranosus arises
from a special rudiment in close association with the sciatic por-
tion of the M. adductor magnus (Bardeen). In a 20-mm. embryo
the tendons of origin and insertion are already developed (Figs.
348, 357). The M. semiteudinosus, according to Bardeen, arises

DEVELOPMENT OF THE MUSCULAR SYSTEM. 499

from two separate rudiments corresponding to its two nerves.
G-riifenberg, however, finds but a single rudiment. The muBcle is

Nn.U.op.l. N.H

0, 35".— (Aflsr Bardeen.) l>oep m

well differentiated in a 20-mm. embryo, but its tendon of insertion

is attached relatively more distally on the tibia than in the adult.

The caput longum, M. biceps femoris, arises from a special

rudiment near the tuber isehiadicum closely fused with that of

500 HUMAN EMBRYOLOGY.

the M. semi tend! Qosus. The caput breve arises as a separate
rudiment continuous proximally with the M. glutffius maximus and
extends distally along tlie fibular margin of the femur. In a
14-mm. embiyo it begins to fuse with the caput longum {Figs.
356, 360).

The Extensors of the Foot. — During the sixth week the rudi-
ment of the peroneal muscles becomes separated from the long

Fio. 3S1I.— (After Bmrdecn.) Deep mua

Pi<;. 3(iO.— (After Banlwo.) D«p musdo of the thigli vl a SO-tnm. embryn.

extensors of the toes and the M. tibialis anterior, and at the same
time the rudiment of each peroneal muscle begins to become dis-
tinct (Figs. 361, ^62). They differentiate in situ, gradually ex-
tending from the dorsolateral surface of the proximal end of the
fibula. The tendon of insertion of the M. peronseus longus gradu-
ally differentiates: in a 14-mm. embryo it can be traced to the
base of the fifth metatarsal, in a 20-mm. embryo part way across
the sole of the foot, and in a 30-mm. embryo to the first metatarsal,
but not until later does the tendon become free in its sheath. The

DEVELOPMENT OF THE MUSCULAR SYSTEM. 501

tendon is at first lateral to the rudiment of the malleolus lateralis ;
later (20 mm.) it passes behind it. The muscle also extends
proximally to the tibia attachment. The M. peronaBus brevis arises
relatively more proximal than in the adult position and its tendon
splits off from that of the peronaeus longus. Schomburg describes
an intimate union between it and the M. extensor digitorum brevis
persisting until the third month, but Bardeen was imable to find it.

In the early stages (Figs. 337, 353) the common extensor
mass of the foot is connected with the peroneal mass, but in a
14-mm. embryo the two masses have become distinct and the ex-
tensor mass has already differentiated into the Mm. tibialis an-
terior, extensor digitorum longus, and extensor hallucis longus
(Figs. 338, 339, 346, 361, 362). The Mm. tibialis anterior at this
stage can be traced into a broad tendon as far as the region of
the OS cuneiforme primum, and in a 20-mm. embryo it has the
adult attachments (Figs. 338, 339, 346, 361, 362). The M. extensor
digitorum longus is differentiated from the central portion of the
muscle mass and is relatively more on the fibular side than in
the adult. At first it ends distally in a broad flat plate which
later, in a 20-mm. embryo, gives off the broad tendons to the
digits. According to Schomberg (1900), the M. peronaeus tertius
is early distinct from the M. extensor digitorum longus, but Bar-
deen maintains that it later splits off from the M. extensor digi-
torum longus with which it is often fused in later life. The M*
extensor hallucis longus early splits off from the deep portion
of the extension mass, although its tendon remains longer fused
with that of the M. extensor digitorum longus. The M. ext. dig.
brevis differentiates in Mtu beneath the extensor plate somewhat
later than the other extensor muscles of the fo6t (Figs. 346, 361).

The Flexors of the Foot. — In an 11-mm. embryo the common
flexor mass begins* to show signs of differentiation into the muscle
rudiments (Figs. 347, 352). In a 14-mm. embryo the two muscle
groups are fairly distinct, a superficial, proximolateral group for
the Mm. gastrocnemius, soleus, and plantaris, and a deep, more
medial group for the Mm. flex. hal. long., flex. dig. long., popliteus,
and tibialis posterior (Figs. 363, 364). The gastrocnemius group
is connected with the blastema of the calcaneus and the two long
flexor muscles with the flat aponeurotic ** foot-plate, " from which
tendons extend to the blastema of the digits. The gastrocnemius-
soleus group gradually spreads from its original lateral position
towards the medial side of the leg to attain the tibial attachment,
and the two heads of the M. gastrocnemius develop during the
second half of the second month, the medial head attaining its
attachment later than the lateral (Figs. 348, 365, 366). The M.
plantaris seems to split off at a comparatively late stage from
the lateral head of the M. gastrocnemius.

502 HUMAN EMBRYOLOGY.

The M. popliteus probably develops in situ from the proximal
end of the deep flexor mass. It is well developed in a 20-mm.
embryo (Figs. 363, 366). The rudiment of the M. flexor hallucis
longus is quite distinct in a 14-mm. embryo {Fig. 364). It dif-

ferentiates from the lateral side of the deep flexor mass, ending
distally at this stage in the common tendon plate from which its
tendon differentiates at a considerably later stage. The M. flexor
digitorum longus is differentiated from the medial portion of the

ii.— (After Bnrdee

deep flexor mass in a 14-mm. embrj'o, and ends distally in the
common tendon plate from which the tendons are beginning to
radiate to the digits (Figs. 348, 36.3). The tibial attachment does
not begin to take place until the embryo is about 20 mm. in length.
The M. tibialis posterior differentiates from the deeper tibial
part of the deep flexor mass over the lower half of the tibia and

DEVELOPMENT OP THE MUSCULAR SYSTEM. 503

extends later Id a proximolateral direction. Its tendon is early
differentiated.

The Plantar Muscles. — The rudiment of the M. quadratus
plantie has dififerentiated in a 14-mm, embryo. Sehomburg (1900)
finds it fused with the M. flexor hallucis longus, but Bardeen did

N. plant. IbI.
Fig. 303.— (After Bardeen. I MubcIw of the eruB ot a l*-iDra. rmbr>-o.

not find this attachment. The M. abductor digiti quinti differen-
tiates at the same stage immediately distal to the tuber calcanei
and later moves to a more lateral position (Figs. 364, 366).

The Mm. flexor brevis and opponens digiti quinti arise from a
common rudiment somewhat later than the above muscles, and
even in a 20-mm. embrvo thev are not clearly differentiated (Fig.
366).

Firi. 3W.— (After Bnnleen.l Huwie" oE tlie cruB of a H-miii. embryo.

The Mm. interossei develop on the plantar surface and the
dorsal interossei wander between the metatarsals to the dorsal
surfare: Ruge (1878), Sehomburg (1900). They first appear in
embryos over 20 mm. in length (Fig. 366).

The M. adductor hallucis arises at the base of the second
metatarsal and wanders to its adult position (Ruge, 1878), and,
according to Ruge, the transverse and oblique heads arise from
a common rudiment, but, according to Sehomburg (1900), from
separate mdiments.

504 HL'MAN EMBRYOLOGY.

The Mm. lumbricates do not ditferentiate until late, in em-
bryos over 20 mm. in length, and, according to Sehomburg, develop
as separate rudiments near the distal extremities of the metatar-
sals and wander towards their attachments to the tendons of the
M. flexor digitomm longus. They arise from the medial plantar
layer.

The M, flexor digitomm brevis develops relatively late. In
a 20-mm. embryo the rudiment is just beginning to differentiate
on the surface of the tendon plate of the long flexor muscles over
the middle cuneiform cartilage (Fig. 365). Its tendons develop
later, as does its proximal extension to the tuber caleanei.

DEVELOPMENT OF THE MUSCULAR SYSTEM. 505

The M. abductor hallucis also develops relatively late. In
a 20-mm. embryo it can just be distinguished on the medial edge
of the plantar surface of the foot in close association with the
M. flexor hallucis brevis (Figs. 365, 366). With the torsion of
the foot the abductor extends proximally to be attached to the
tuber calcanei.

The M. flexor hallucis brevis, like the other muscles in this
group, only begins to appear in a 20-mm. embryo (Fig. 366);
later it splits into two parts, the lateral head coming into relation
with the M. adductor and the medial with the M. abductor hallucis.

THE MUSCLES OF THE HEAD.

Muscles of the Orbit. — It has commonly been assumed that the
muscles of the orbit are derived from anterior head somites ; the
first somite giving rise to the Mm. levator palpebrsB superioris,
rectus superior, rectus internus, rectus inferior, and obliquus in-
ferior, supplied by the N. oculomotorius ; the second, to M. obliquus
superior, supplied by the N. trochlearis; and the third, to the
M. rectus lateralis, supplied by the N. abducens. Anterior head
somites have, however, never been observed in man or mammals.
Zimmermann (1898) observed in a 3.5-mm. embryo several small
head cavities in the region where later the eye muscles develop.
It is uncertain even that they represent rudimentary head somites,
and no connection has been established between them and the
eye muscles. On the contrary, the observations of Renter (1897)
on the i^ig and my own observations on human embryos, which
follow here, show that all the eye muscles arise from a common
premuscle mass, which occupies, both in the pig and in man, the
same general position in the early embryo. This common pre-
muscle mass is first to be recognized in human embryos of about
7 mm. in length (Fig. 367). It consists of a lens-shaped mass of
condensed mesenchyme, outlined from the surrounding mesen-
chyme by a capillary network over its surface. This premuscle
mass lies dorsal to the optic stalk, between it and the ganglion
Gasseri, and medial to the optic cup. The N. ophthalmicus passes
in front of and lateral to the mass, and the N. maxillaris behind
and lateral to it. At this stage only the N. oculomotorius enters
the anterior end of the muscle mass. The Nn. trochlearis and
abduceus do not appear until later.

In a 9-mm. embryo the eye premuscle mass occupies much
the same position as in the earlier stage, lying on the dorsal side
of the optic stalk and medial to the N. ophthalmicus and maxillaris
(Figs. 368, 369). It has enlarged somewhat and extends along
the caudal side of the optic stalk. It also begins to show cleavage
into separate muscle masses, each supplied by its respective nerve.

606 HUMAN EMBRYOLOGY.

The N. trochlearis now enters the anterior portion of the mass
which later forms the rudiment of the M. ohliquns superior. The
N. abducens enters the caudal end of the mass, which has begun
to extend out along the path of the nerve and also shows indica
tions of separation from the rest of the mass which lies closer
to the optic stalk and into which the N. oeiilomotorius runs. The
muscle mass at this stage has no very distinct attachment either

Fia. 367. — Embryo 7 mm. id lenstli. Dikcnm with pnmuMle Tn«WM of tiie head and ulterior myotomca;
from model.

to the precartilage or to the sclera, but there exists a direct con-
tinuity with the mesenchyme from which tliese structures differ-
entiate.

In an 11-mm, embryo the premuscle mass has still farther
enlarged and partially split into the rudiments supplied by the
three nerves. The anlagen lie on the dorsal and caudal sides of
the optic nerve and for the most part medial to the eyeball (Figs.
370, 379). They are continuous laterally with the primitive sclera,
which is now beginning to form as a definite condensation of the
mesenchyme about the eyeball, and medially with the precartilag-

DEVELOPMENT OP THE MUSCULAR SYSTEM. 507

M.VI

H. disphrwfmB Mm. inrrahyokleua
Fig 3<i9.— Embryo 9 mm. in length. Prfinui<cLe iqskwh of thf «>«. 1on«ue, infrahyoid, and tliaphnc°>

inous tissue about the optic nerve. The M. rectus lateralis has
extended farther out along the path of the N. abducens and has
as yet no skeletal attachment. The N. ophthalmicus passes above
these muscle masses and nearly at right angles to them.

508 HUMAN EMBRYOLOGY.

As differentiation progresses tlie muscle mass of the N. ocu-
Jomotorius gradually extends around the optic nerve and splits
into the various muscles supplied by this nerve. In a 14-mm.
embryo all the orbital muscles are to be distinguished and have
nearly the adult relations to the bulbus oculi. The M. obliquus
inferior, however, does not completely separate off from the M.
rectus inferior until a later stage.

The Muscles of the Mandibular Arch. — The mesoderm of the
mandibular arch gives rise to the muscles of mastication, includ-
ing the Mm. temporalis, masseter, pterygoideus externus and io-

Fio, 370.— Embryo II mm. in letisth. rKa^nun of musdw of the head iind neck, fromsraphic recoDslrao-

temus, and probably to the M. mylohyoideus. The Mm. tensor
tympani and tensor veli palatini are also derived from this arch.
In a 7-mm. embryo the mandibular arch is filled with a uniformly
closely packed mesenchyme, with only the slightest trace of con-
densation about the peripheral end of the N. mandibularis (Fig.
367). In a 9-mm. embryo, however, this condensation is clearly
to be recognized (Fig. 368). This preranscle mass, in which the
N. mandibularis ends, lies at about the middle of the arch. It is
a simple mass, without indications of splitting and not sharply
outlined from the mesenchyme which fills the arch. In an 11-mra.
embn-o this egg-shaped i)remuscle mass has increased in size, but

DEVELOPMENT OF THE MUSCULAR SYSTEM. 509

still shows no indications of splitting into the various muscles
(Fig. 370). The differentiation probably takes place in a manner
very similar to that described by Eeuter in the pig. The pre-
muscle mass is from the very beginning closely associated with
the condensed mesenchyme for the mandible, and with the dif-
ferentiation of the proximal end of the mandible the premuscle
mass is partially split into a Y-shaped mass, the handle repre-
senting the M. temporalis, the outer limb corresponding to the
M. masseter, and the inner deeper limb, separated from the outer
by the proximal end of the mandible, the mass for the Mm.
pterygoideus externus and internus. In a 14-mm. embryo this
process of differentiation has progressed still farther, and the
Mm. pterygoideus externus and internus are partially separated
by Meckel's cartilage. The processus coronoideus only partially
separates the masseter from the pterygoid mass at this stage.
With the continued differentiation of the membranous mandible
and adjoining portions of the skull to which the muscles of mas-
tication are attached comes the gradual differentiation of these
muscles. The muscle:: are at no time attached to Meckel's carti-
lage, but are always in relation with the membranous mandible.
In a 20-mm. embryo the various muscles of mastication are easily
to be recognized, but have only a slight resemblance to the
adult form. The M. temporalis is very small in proportion to
the size of the head and gradually extends over a much greater
proportional area during later stages. The M. masseter is at
first attached only to the medial and lower surfaces of the arcus
zygomaticus.

The M. mylohyoideus apparently differentiates more rapidly
than the other muscles of mastication, and is to be recognized
by its nerve supply in an 11-mm. embryo, and in a 14-mm. embryo
it has much the adult relations. I have been unable to determine
its origin from the common muscle mass.

In a 14-mm. embryo the Mm. tensor tympani and tensor veli
palatini are to be recognized and are connected with the pterygoid
mass from which they probably arise. The M. tensor tympani
has already gained its insertion to the malleus. The later de-
velopment of these muscles is bound up with the development
of the base of the skull, the tuba auditiva, and the soft palate.

The Facial Muscles {The Muscles of the Hyoid Arch.) — The
facial muscle group includes all the muscles supplied by the N.
facialis. The subcutaneous muscles of expression and certain
muscles about the facial openings concerned with the vegetative
functions belong to this group.

Futamura (1906) has given the most elaborate recent account
of their origin and development, and the following is based upon
his work.

510 HUMAN EMBRYOLOGY.

This entire facial musculature arises from the closely packed
mesenchyme which fills the second branchial or hyoid arch. In a
9-mm. embryo the main stem of the N. facialis, which is very
simple at this stage, passes into the hyoid arch to end brush-like
in a single mass of premusele blastema that occupies the ventro-
lateral portion of the arch (Figs. 367, 368, 371). The condition
is very similar to that described by Futamura as existing in a
10-mm. embryo. It is from this premusele mass that the entire
musculature supplied by the N. facialis arises (Futamura). This

Flo. 371.— (After FuUmum, Aiut. HefW, Bd. 30. Fic- 27, on p. 440.) iiumaii cmbtyo. 27-30 dai?.
XSD di&. SucitCBl projection from fronUl Hietioai. a. eye; Cv, guiglJDD triganiDi: (i, <ii, Uu. runiu
primus, MGimdiu. and tertiiu N. trifemtni; ^, juncdoD of Xhx r. u N. triganioi with N. petroflus supcjf.
maj.; f, N. linsuaJii; Cj., chorda tympani ; JV.p.t, nuv'.. N. petroaue (uperfidalU major; G.vii, gHiflioo
*■ " " .. .. . ^ . . ^ .. ^ jToBHOpharynB'*:

premusele mass increases in size (Fig. 370), and in an embryo
13.7 mm. in length has begun to spread out not only ventralwards
but also dorsalwards and aborally (Fig. 372). It also extends
towards the shoulder to form the platysma. The medial side of
the mass becomes thickened to form the rudiment of the Mm.
stylohyoideus, digastricus, and stajwdius. It extends from the
root of the tongue along the posterolateral side of Beichert's
cartilage towards the ear capsule.

As the muscle rudiment spreads out the N. facialis becomes
divided into several branches which follow the wanderings of the
muscle tissue. Thus, in a 13.8-mm. embryo the nerve stem distal

DEVELOPMENT OF THE MUSCULAR SYSTEM. 511

to the chorda t>'mpaiii divides into three branches, a thin one
directed medially into the rudiment of the Mm. digastrieus and
stylohyoideus, a second large branch, the N. auricularis posterior,
and a third large branch which soon divides into the R. temporalis,
maxillaris, and cervicofacialie.

In a 15.5-mm. embryo the platysma rudiment has extended
orally over the hyoid arch and caudally to the region of the
sternum and shoulder-girdle. It has also pushed medially and
begins to unite with its fellow of the opposite side (Fig. 373,

Fio. 372. — (After FuUmum, Aiwt. HefM, Bd. 30. Fig. 2, on p. 441.) Huroui ambryo of 31-34 days.
Sagittal projeeliDo rrom aacittal series. XSSdis. EipluationssiD Gsurs 371. fi.p.i.miit., N.petrtma

374). The spreading of the muscle headwards takes place along
two paths, separated by the aniage of the outer ear. The occipital
portion gives rise to the Mm. auricularis posterior, transversus
nuchfe, transversus and obliquus auriculie, but at this stage still
forming a continuous membrane.

The facial portion of the platysma splits at the upper part
of the neck into two layers, a superficial, lightly staining one
and a deeper, more intensely staining one. A capillary network
often separates the two layers. Futamura designates the super-
ficial layer as the platysma faciei and the deep layer as the
sphincter colli.

The platysma faciei gradually extends over the lower jaw and

512 IIL'JIAX EJIBEYOLOGY.

cheek to the forehead, eye, and temporal region, while the most
anterior part goes to the lower lip. At the angle of the mouth
the two layers are very difficult to separate from one another.
In a 7-wk. embrj'o (Figs. 375, 376) the platysma faciei over the
side of the head and ahove the ear unites with the platysma
occipitale, which has also in the meantime extended cranialwards
and broadened out to touch its fellow on the opposite side. The
piatj-sma occipitale has, however, now lost its connection with the
platysma colli.

Pio.973.— (A/t«rFut«miirm,An«t.Hott«,Bd.30.riB.4,A,onp.4. ,
SacitUtI proieclion from frontal wria. X20 d>a. Deep layer, ojk.. ortncul«rii oculi: g
nfen; Qj-t.p., theanbi^ of the M. quadrmtuB ^bij fluperiohe proprjUB; a, the partji or Che flphinet^ cQlti
soiog to the lower letenJ ode of the eye; 0.ar., orbiculima owie; a.a., orbicularU auHcuIif: N js.p,, oervuB
auHcularis poeterior; b' utd b". bnncha uF the faciei goini Is the posterior end anterior nirfaca of the
-eAr; RA.f., runiu t^npomfaeiaiiB; Rxj,, ramus oervioofacialia; tj.. Bphiocter colli.

The sphincter colli, the deep layer, which imderlies the
platysma faciei, forms at first by the sixth week a sheet over
the face, with sphincter-like differentiations about the mouth, nose,
eye, and ear, to form the primitive Mm. orbicularis oris, orbicularis
narium, orbicularis oculi, and orbicularis auriculae (Fig. 373). The
differentiation of the sphincter colli begins earlier than the super-
ficial layer and is far advanced in embryos 8-9 weeks old(Fig. 378).
The lateral portion of the sphincter colli over the cheek degener-

DEVELOPMENT OF THE MUSCULAR SYSTEM.

513

ates, as do also the primitive Mm. orbicularis oculi and narium.
That part of the sphincter colli between the M. orbicularis oculi
and angle of the mouth becomes attached to the maxilla to form
the rudiment of the M. quadratus labii superioris. Lateral to this
the M. zygomati<ius appears to develop from the sphincter colli.
The M. orbicularis oris, which comes from this layer, continues
to increase in size and, connected with the mouth but having attach-
ment to the skeleton, are differentiated from the sphincter colli

Fia. 374.— <Aft«r Fuuunurs, Aunt, tlefw. Bd. 30. Fig. 4. B. on p. 44fi.) SuperSdkl layer of the
culsture of the nine embryo as in Fit. 373. pji., platysou occj|»(«le: «, onl foaea: p./.,
i: P.C.. pUtyBom colli.

the Mm. eaninns, incisivus labii superioris and inferioris, and
nasalis. The latter replaces partly tlie M. sphincter narium. The
M. triangularis is associated with the M. caninus. The M. risorius
is derived later {thirteenth to seventeenth week) from the M.
triangularis. The M. buccinator is derived from that portion of
the sphincter colli l>ing between the upper and lower lips, and
as the mouth decreases in size the muscle comes to lie deeper.

The superficial layer, the platysma faciei, spreads out over
the face and head in a continuous sheet, and in a Z-weeks embryo
has united over the ear with the platysma occipitale to form the
M. fronto-auriculo-occi pi talis (Fig. 375). As the sphincters of

Vol. I.— 33

514

HUMAN EMBRYOLOGY.

the deep layer degenerate, there are gradually formed out of the
superficial layer a new orbicalaris oculi and orbicularis anricolse
(Figs. 375, 377). The medial and lateral part of the M. quadratus
labii superioris is derived from this superficial layer and also the
Mm. mentalis and quadratus labii inferioris (Fig. 377). From the
M. fronto-auriculo-occipitalis are derived the Mm. auricularis sa-
perior and anterior, and, through degeneration of the medial por-

Pio. 3TG.— (AfterFuUuaurm Anftt. Herie, Bd. 30, Fig.6.A.onp.44B.) Superficial layer of th<
embryo u ia Fig 376. Fji.o^ M. FronU>4uriculo-occipitALis; o.oej>„ U. orbicul&ria oeuLi (Inun

"": AJ.. R. Umporalia: I.U., H. levalor Isbii auperiorifl proprius (alKque mui); Ojir., orb
ona; A, max., R. mAxillariB; R. mar., R. morgiDalifi; R. fot^, R. colli; R.c.f., R. MrrviiyifAciKJiv; b"
the branchefl of the facial nerve coinK to the antvriar and pofftehor Burfaocfl of tJie ear; o
aurioul)E; H.a,p^ R, suriculAris poctcrior.

tion of the M. fronto-auriculo-occipitalis, the Mm. frontalis and
occipitalis become widely separated but joined by the galea
aponeurotica which probably represents the degenerated portion
of the muscle.

From the platysma occipitalis not only arises the M. occipitalis
but also the Mm. auricularis posterior and transversus nuchie
through degeneration of the intermediate parts.

It has already been noted, that on the medial side of the
platysma arise the rudiments of the Mm. digastricus and stylo-

DEVELOPMENT OP THE MUSCULAR SYSTEM.

515

hyoideus. In the sixth week this mass is already well developed,
extending from the posterior side of the otic capsule in a concave
bow towards the angle of the lower jaw. At this stage it is in
intimate relation with Eeichert's cartilage. With the growth and
lengthening of Beichert's cartilage comes the complete separation
of the digastric rudiment from the platysma. In the early stages
this anlage is supplied entirely by the N. facialis, the N. mylo-

Fio. 376. — (AfUr Pulsmuis, Askt. HeTle. Bd. 30, Fig. 6. B, on p. tlSO.) Humaii «mbryo o( 7 weekn.
8B(itt«l pnjsotioa Iram fronlal Kctions. X 12 dia. Deeij layer, o-t., U. arUeularis oouli (From iphinctsr
oolli); mJ.. U. mBxillolsbiBles; o.or., M. orbiculariB nris: buc.. M. buccinslor: oin.. H. eaninuB; tv„ M.
lygODUitiouBi «.c., aptuDctar cidli: Sjv., R. lygmutieua; R. buc., R. buceiiuitoriiu; N,a,p., N. niuicularis
p<Mt«rior, RJ., R. lempontlis; Aj;./.. R. nrvioolsculis; A.iRai..R.auiillaris.

hyoideua entering only the M. mylohyoideus. At first the M.
digastricus consists of only a single belly. From this rudiment
splits off gradually the M. stylohyoideus. Parallel with this
process occurs a constriction and degeneration in the middle of
the digastricus, dividing it into two bellies. During the eighth to
ninth week this process is quite complete. The innervation of
the anterior belly of the digastric by the N. mylohyoideus is first
to be recognized in a 7-weeks embryo when the tendon begins to
form.

S16 HUMAN EMBRYOLOGY.

The M. stapedius appears to come from the proximal end of
the rudiment of the M. digastricus. It gradually becomes separated
and enclosed within the otie cartilages. In a 14-miii. embryo it
is quite separate from the digastric and lies in close relation to
the stem of the N. facialis.

The Mm. levator veli palatini and uvulie arise from the facial
mass. Their development and complete separation from the rest
of the facial muscles are bound up with the development of the

Fro. 377.— f After Fuuununi. Anat. Hefte, Bd. 30. Fii. S. A, on p. 456.) Human fetus of 84 meki.
Sagittal projection from nsittal seriea. X 14 dia. Superfieial layer of Ihe fadal miuculalure. t.a.o^
U. frontt>-auncuk>-occipJl«ILi>: ox,. M. orbleularin oruli: U.;, M. levator lalni njperioris stcque nasi;

H. indsivuB Ubii inlerioris; r., M. triaD«utarii<; Pj.. platynna «tli: a.p,. M. aurieularis poeterior: oji^
orbiculans auriculs: N.a.p.. auricularis pwterior: Rj., ramus tanparaJis; R.c, ramus colli: S.mar,

palate and the tuba nuditiva. The M. uvulie is at first a paired
muscle, but with the formation of the soft palate the two muscles
unite in the midline.

The Pharyngeal Muscles. — Very little is known concerning
the development of the pharyngeal muscles, but the constrictors
of the pharj-nx, as well as the Mm. stylopharyngeus and palato-
glossus, probably arise from the third gill arch. The premuscle
tissue of this arch is already recognizable in a 9-mm. embryo
and into it goes the ninth nerve. The third and fourth gill arches
at this stage have already sunken some distance below the sur-

DEVELOPMEiNT OF THE MUSCULAR SYSTEM.

517

face, and thus the premuscle mass comes to lie in the depths in this
region. In an ll-mm. embryo the Mm. stylopharyngeus and con-
strictors are closely united together at the side of the pharynx,
the M. stylopharyngeus having its attachment to the precartilag-
inous horizontal styloid process near its medial end. With the
growth and shifting of the various structures in this region this
portion of the styloid gradually assumes a more lateral position,

FiQ. 378.— (AftM Fulamu™, Anst. Hrfte. Bd. 30, R*. 8, B, on p. «7.) Deep Uyw of the r&ci*!
miuculstureof tb«Mme«nbryouiDFil.377, withhighermaanificAtion. mn.. M.caninus: n., M.DBBBlis;
i.lj,, H. iordsivus labii superioria; bae„ M. buccinator; (^ trianEulu-is (abceschnittea); iJ,i,, incisivua
labii inr«riorie; ({i.t., M. qiudntui Isbli inferioiis; m., meoUiU.

and in a 14-mm. embryo the muscle takes a medial direction toward
the thyroid precartilage and the constrictors. One can also dis-
tinguish at this stage the attachment of the M. constrictor
pharyngis medius to the hyoid and the M. constrictor pharyngis
inferior to the thyroid cartilages. These two constrictors are
still united into a common mass which is rapidly extending over
the dorsum of the pharjoix. Concerning the M. constrictor
pharjTigis superior nothing is known and I am uncertain as to

618 HUMAN EMBRYOLOGY.

whether it arises in common with the others. Its relation with
the buccinator suggests that it may arise from the facial mass.
The M. constrictor pharyngis inferior is at first continuous with
the M. cricothyreoideus. In a 20-mnL embryo the pharyngeal
muscles are quite distinct and the constrictors have grown round
to the mid-dorsal line of the pharynx.

The Intrinsic Muscles of the Larynx. — The muscles of the
larynx probably arise from the ventral ends of the third and fourth
gill arches, which early fuse to form a mass of closely packed
mesenchyme out of which later diflferentiate the cartilages and
muscle*. Soulie and Bardier (1907) found it difficult to recognize
laryngeal muscles in a 14-mm. embryo. But in a 19-mm. embryo
they were able to recognize clearly the Mm. interaryta^noideus,
crico-arytsenoideus posterior, cricothyreoideus, and thyreo-crico-
arytaenoideus. They were unable to discover any traces of a
sphincter laryngis as described by Strazza (1889), but found that
in 32- to 40-mm. embryos the M. thyreo-crico-arytsBuoideus is
clearly distinguishable from the M. thyreo-arytaenoideus and
towards the middle of the fifth month all the muscles are recogniz-
able.

I have noticed that in a 14-mm. embryo one can distinguish
the various muscles, the Mm. arytaenoideus, crico-arytsenoideus
posterior and lateralis, thyreo-arytaenoideus, and the crico-
thyreoideus. I do not find, as Strazza, the muscles forming a
common constrictor of the larynx. I find, with Strazza, that the
constrictor of the pharynx is continuous with the M. crico-
thyreoideus. With the farther differentiation of the cartilages the
muscles become more distinct and in a 20-mm. embryo they have
much the adult form.

The Tongue Musculature. — It is usually assimaed that the
tongue musculature is derived from the occipital myotomes which
appear to be serially related to the N. hypoglossus. There is,
however, no direct evidence whatever for this statement, and we
are inclined to believe from our studies that the tongue muscula-
ture is derived from the mesoderm of the floor of the mouth. In
a 7-mm. embryo the mesenchyme in the floor of the mouth is
similar to that in the mandibular and hyoid arches from which
later the musculature of these two arches develops. In a 9-mm.
embryo the floor of the mouth has increased in thickness and
the groove between the mandibular and hyoid arches has disap-
peared. In the mesenchyme of this thickened floor are two
bilateral masses similar in appearance to the jaw and facial masses
found in the mandibular and hyoid arches at this same stage.
These bilateral tonsrue premuscle masses extend from the region
in which the mandible later develops to the hyoid region, and
are here continuous with a medial mass of condensed mesenchyme
which extends into the larynx region and also with the infrahyoid

DEVELOPMENT OP THE MUSCULAR SYSTEM. 519

premuscle bands {Fig. 369). The caudal end of this latter mass
is in turn continuous with the diaphragm premuscle mass. This
lingual-infrahyoid-diaphragmatic band is probably a primitive
ventral visceral muscle complex and in no way concerned with the
myotomic system. The N. hj-poglossus enters the caudal end of
the tongue premuscle mass. One is unable at this stage to dis-
tinguish any of the individual muscles.

In an 11-mm. embryo (Figs. 370, 379) each homogeneous
premuscle mass has split into two masses, a medial ventral mass
for the Mm. geniohyoideus and genioglossus and a dorsolateral

mass for the Mm. hyoglossus, styloglossus, and chondroglossus.
The medial ventral mass extends from the region of the future
symphysis menti to the prehyoid mass and dorsally it expands
into the tongue region. The main stem of the N. hypoglossus
enters its caudal end and passes longitudinally nearly to the an-
terior end. The dorsolateral mass extends from the prehyoid
and medial portion of the styloid process into the dorsolateral
region of the tongue for a short distance. A branch of the N.
hypoglossus enters its ventral surface. The styloid process at
this stage has very nearly a horizontal position and extends
nearly to the midline.

520 HUMAN EMBRYOLOGY.

With the differentiation and development of these muscle
masses the tongue gradually becomes raised more and more above
the mandibular arch. In a 14-mm. embryo this process is ad-
vanced, keeping pace with the differentiation of the mandibular
arch in which are now plainly to be recognized Meckel's cartilage
and the partially enclosing membranous mandible. From the
membranous mandible arise the radiating M. genioglossus,. extend-
ing a considerable distance fan-like into the tongue, and the M.
geniohyoideus, extending to the hyoid precartilage. Over the
dorsum and dorsolateral region of the tongue extend the M. hyo-
glossus and M. styloglossus, from the hyoid precartilage and
styloid process respectively, to the tip of the tongue. They lie
dorsal and lateral to the radiating genioglossus. Their origins,
though distinct, are still close together and parallel. The N. hypo-
glossus gives off branches to the M. geniohyoideus, then to the
Mm. hyoglossus and styloglossus, and passes through the M.
genioglossus to its tip, giving off numerous lateral branches into
this muscle. There is at this stage apparently very little inter-
lacing of the tongue muscle, nor are we able to recognize either
the intrinsic muscles — the Mm. longitudinalis superior and in-
ferior, transversus linguae, and verticalis linguae — or the M. glosso-
palatinus.

In a 20-mm. embryo, however, all the muscles are clearly dif-
ferentiated and increased in size. The origin of the M. styloglossus
has been carried to a more lateral position and enters the tongue
at an angle to the M. hyoglossus. The latter has spread out more
in its attachment to the hyoid cartilage. The M. glossopalatinus
is now recognizable, extending from the laterally placed soft palate
to the lateral surface of the tongue. The great development of
the intrinsic muscles is most noticeable at this stage, but concern-
ing their origin there are no observations. It is uncertain whether
they are derived from the hyoid and mandibular tongue muscles
or independently from the mesenchymal matrix. At this stage
the interlacing of the tongue musculature is quite advanced.

LITERATURE.

Bardeen: The Development of the Musculature of the Body Wall in the Pig,
Including its Histogenesis and its Relation to the Myotomes and to the
Skebtal and Nervous Apparatus, Johns Hopkins Hosp. Rep., vol. ix, 1900.
Development and Variation of the Nerves and the Musculature of the
Inferior Extremity and the Neighboring Regions of the Trunk in Man,
Am. Journ. of Anat., vol. vi, 1907.

Bardeen and Lewis: Development of the Back, Body Wall, and Limbs in
Man, Am. Journ. of Anat., vol. i, 1901.

Collin: Recherches sur le developpement du muscle sphincter de Tiris chez les
oiseaux, Bibliographic Anatomique, t. 12, p. 183, 1903.

DEVELOPMENT OF THE MUSCULAR SYSTEM. 521

Felix: Teilungserscheinungen an quergestreiften Muskelfasem menschlieher Em-

bryonen, Anat. Anz., Bd. 2, 1888. Ueber Wachsthum der quergestreiften

Muskulatur naeh Beobachtungen am Menschen, 2^itschrift f . wiss. Zool., Bd.

48, p. 224, 1888.
FiSCHEL, A.: Zur Entwieklung der ventralen Rumpf u. Extremitatenmuskulatur

bei Vogeln und Saugetieren, Morph. Jabrbuch, Bd. 23, 1895.
Futamura: Ueber die Entwieklung der Faeialismuskulatur des Menschen, mit

27 Textabbildungen, Anat. Hefte, Bd. 30, 1906.
€U)DLEWSKi : Die Entwickelung des Skelet- und Herzmuskelgewebes der Saugetiere,

Archiv f. mikr. Anat., Bd. 60, 1902.
Grafekberg, E. : Die Entwieklung der mensehl. Beckenmuskulatur, Anat. Hefte,

Bd. 23, 1904. Die Entwieklung der Knochen, Muskeln und Nerven der

Hand und der fiir die Bewegungen der Hand bestimmten Muskeln des

Unterarms, mit 19 Abbildungen im Text, Anat. Hefte, Bd. 30, 1905.
Harrison, R. G. : An Experimental Study of the Relation of the Nervous System to

the Developing Musculature in the Embryo of the Frog, Am. Joum. of

Anat., vol. iii, 1904.
Heerpordt, C. F.: Studien ueber den Muse. Dilatator Pupillae, etc., Anat. Hefte,

Bd. 14, p. 487 to 558, 1900.
Heidenhain, M. : Ueber das Vorkommen von Intercellularbriicken zwischen glatten

Muskelzellen und Epithelzellen, etc., Anat. Anz., Bd. 8, 1893.
Herzog, H. : Ueber die Entwieklung der Binnenmuskulatur des Auges, Archiv f.

mikr. Anat., Bd. 60, p. 517-586, 1902.
Ingalls, N. W. : Beschreibung eines menschlichen Embryos von 4.9 mm., Archiv f .

mikr. Anat., Bd. 70, 1907.
Kotzenberg, W. : Zur Entwieklung der Ringmuskelschicht an den Bronchien der

Saugetiere, Archiv f. mikr. Anat., Bd. 60, p. 460, 1902.
Kazzander: Beitrag zur Lehre ueber die Entwieklung der Kaumuskeln, Anat.

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Keibel, F. : Studien zur Entwicklungsgeschichte des Schweines II. Morphologische

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Archiv f. Anat. u. Phys., Anat. Abt., 1891.
Kroesing: Ueber die Riickbildung und Entwieklung der quergestreiften Muskel-
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522 HUMAN EMBRYOLOGY.

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Bd. 53, 1899.

XIII.
CCELOM AND DIAPHRAGM.

By franklin P. MALL.

The small ovum described recently by Bryce and Teacher is
hardly two millimetres in diameter, and is covered with a reticular
mass of syncytium, true villi with mesodermal cores not being
present. Within there is an extremely small embryo anlage
embedded in a delicate cellular reticulum. The mesenchymatous
tissue shows no signs of cleavage into a parietal and a visceral
layer nor has it arranged itself into a denser layer around the
wall of the vesicle. The general appearance of the mesoderm is
shown in Fig. 10, Chapter IV, and in Fig. 93, Chapter VII. It is
there seen that no exocoelom is present. In comparing this speci-
men with Peters^ ovum, which is somewhat larger, we must
imagine a destruction of some of the mesodermal tissue, either in
the centre of the ovum or near the embryo, in order to form the
primitive exoccelom. In fact this interpretation can be given to the
form of the exoccelom in Peters' ovum, as is shown in Figs. 96 and
97, Chapter VII. The first figure is taken from Peters' plate,
and the second is an interpretation of this figure by Professor
Grosser, who has compared the section from which the Peters
drawing was made with the drawing itself. It is seen, therefore,
that the exoccelom is not present in an ovum two millimetres in
diameter, and that it is well formed in an ovum somewhat larger,
that is, at the beginning of the third week of pregnancy.

All the other young human ova which have been studied by
embryologists, possibly including that by Peters and those by
Graf Spee, have within them a large cavity lined entirely with a
layer of mesoderm. The precocious development of this space,
the exocoelom, appears to be peculiar to man and monkeys, for it
has not been observed in other mammalian ova which have been
studied with great care in a large number of species. Han^ng
freely within this cavity, but attached to one side of the chorion,
there is always found in normal ova a relatively small embryonic
mass composed of a closed amnion and an umbilical vesicle joined
together by the anlage of the embryo, which in the youngest speci-
mens contains only the three primitive blastodermic membranes.
In general the diameter of the embryonic mass is but one-fifth of
that of the exocoelom, which indicates that the latter began to form

523

524 HUMAN EMBRYOLOGY.

by a splitting of the mesoderm when the ovmn was very small^
unless we assume that the embryonic mass becomes absolutely
smaller while the exocoelom is forming. In the Peters ovum the
embryonic mass measures about 0.2 mm. in diameter, and that of
the exocoelom, which is egg-shaped, averages about one mm.

Until the embryo is 2 mm. long the amnion hugs the embryo
closely and does not encroach markedly upon the exocoelom. As
the embryo grows a little larger some anmiotic fluid accumulates
around it, which naturally causes the embryonic mass to grow
much more rapidly than the embryo. During this time the embryo
£dso grows relatively faster than the exocoelom and therefore the
embryo and amnion soon begin to obliterate the exocoelom. At
the time the embrj^o is 4 mm. long the ratio in size between the
embryonic mass and the exocoelom is about 5, and somewhat later
it is but 3. When the embryo measures 7 mm. and the ovum is
18 mm. in diameter, the ratio is 2, and by the beginning of the
eighth week the exocoelom is obliterated entirely. Now the amnion,
lines the entire chorion with the exception of a small region around
the umbilical vesicle which lies inunediately below the chorion and
is surrounded by a small space, the last remnant of the exocoelom.

The exocoelom is filled with an albuminous fluid which is
held together by a delicate network of fibrils and gives it a jelly-
like consistency. This mass, the magma reticule of the older
authors (Velpeau), is also well marked in the exocoelom of
monkeys' ova, and is probably more marked in normal ova than
is generally believed (Keibel). In case the fibrils of the magma
are scanty or beginning to disintegrate, or in case they are greatly
increased in number, dense enough partly to obliterate the embryo,
the specimen is certainly pathological. Magma which is trans-
parent and contains just enough reticulum to hold it together is to
be viewed as the normal constituent of the exocoelom.

The nature of magma fibrils has not been definitely settled,
but they appear to be connected with cells in some way as indicated
in the ova described by Bryce and Teacher and Peters. Some
embryologists are inclined to consider them the product of coagu-
lation. However, they are present in the freshest specimens, and
they cannot be stained by Weigert's fibrin stain. I have found
reticular magma present in normal ova which were preserved in
strong formalin immediately after their abortion. According to
Eetzius, the magma reticule contains fibrils of a muco-fibrillar
nature which become transparent in dilute acetic acid.

Before the circulation of blood is established between the
embryo and the chorion, — that is, before the embryo is 2 mm.
long, — the nutrition of the embryo and its umbilical vesicle must
pass from the chorion through the magma. This may be the

C(ELOM AND DIAPHRAGM. 525

reason why any alteration in the nutrition of the embryo, which
affects its normal development, first manifests itself in a change
in structure of the magma reticule. As the exocoelom is gradually
obliterated the magma is pushed ahead of the advancing amnion
and finally forms a delicate membrane of fibrils between the
amnion and chorion.

BODY CAVITIES.

The coelom of the embryo arises independently of the exo-
ccelom in embryos between 1.5 and 2 mm. long. In specimens
less than 1.5 mm. long studied by Peters, Graf Spee, and Minot,
there is no trace of either blood-vessels or body cavity within the
embryo, but in Graf Spee's well-known embryo Gle. (1.54 mm.
long) traces of the beginning of the

heart and its ccelom are present. Fig. "»■ ■«'■

380, which is through the head of this
embryo, contains on either side of the ^
body a few scattered cells between

the mesoderm and entoderm. These Kd.

Graf Spee believes to be the endothe-
lial anlage of the heart. In this same
section there is a split in the meso-
derm of the embryo, which continues
through other sections and marks the
beginning of the pericardial coelom.
It may be noted that the endothelial ^^^^' ^^■'*„
anlage of the heart and its ccelom (<.«««; eA..ciiori»: m.,eiiwdBrm. thb

- A, iii- J- IIP 1 Apftce In th« [QflHodFrm JA the bcainDinc of

arise after the foregut is well formed- the c«iom, Md betw«n it ^nd tho fnio-
— that is, after the head of the embryo noHii'm^'u!^'™^^' ^"'^ "''''* ''
is separated from the yolk-sac. The

different sections show that the coelom is of irregular form and
size and it is surrounded with numerous dividing cells (Fig. 381).

Since no other human embryo has been studied which follows
immediately upon Graf Spee's Gle., we must fill out the gap by
observations upon other mammalian embryos; these are very
complete and have been made with great care. They do not con-
tradict one another nor any of the observations made upon the
development of the human ccelom. For these reasons much con-
fidence can be jilaced upon facts derived from comparative embry-
ology upon the early formation of the pericardial ccelom and their
bearing upon the same in human embryos.

Bonnet's careful study of the development of the ccelom in
the embryo sheep fills out perfectly the gap between Spee's Gle.
and older human embryos. In the sheep t!ie pericardial coelom
appears as irregular spaces on either side of the head much as in
Graf Spee's embryo Gle. The spaces arise on both sides of the

52e HUMAN EMBEYOLOGT.

embryo, but are so irregular in position and form that their
arrangement can not possibly be considered metameric Next the
spaces unite, thus forming in a relatively short time large spaces
on either side of the body, which soon unite with each other at
the extreme anterior end of the embryo, forming a horseshoe-
shaped canal in the mesoderm on the ventral side of the head.
Throughout its development the pericardial ccelom is closed on its
lateral sides and does not communicate with the exocoelom, with
the exception of its later and indirect communication through the
peritoneal coelom. It may also be noted that in the sheep the
whole pericardial coelom is formed hand in hand with the invagina-

Fio. 381. — Bsction No. 81 tlirouch Omf Spee's snbryo Ola. (Aftar Qrul Spn
wBlmk, near which on the «ntad(niul nda, m fair looM mlla nuy be wen nhii^ i
■nlege of the hou-t

tion of the foregnt and before the endothelial anlage of the heart
has arranged itself into vascular tubes, much as is the condition
found in Graf Spee's embryo Gle.

That the pericardial ccelom arises very early and independ-
ently of the exoccelom is farther proved by the work of Strahl
and Carius, who studied its development in the guinea-pig and the
rabbit and confirmed fully the earlier observations of His upon
the first formation of the pericardial coelom {Parietalhohle). In
the rabbit the pericardial ccelom ends in two dorsal and two
ventral recesses, all four of which connect subsequently with the
peritoneal ccelom. However, only the dorsal recesses break into
the peritoneal coelom in the human embryo, and it is this recess
or canal which later on encircles the lung and probably forms the
main anlage of the pleural ccelom.

We can now return to the human embryo, and the next stage
after Graf Spee's Gle. which bears upon this point is found in
a well-preserved normal human embryo 2 mm. long. The embryo

CCELOM AND DIAPHRAGM. 527

came from a self-inflicted mechanical abortion and was soon pre-
served in formalin. Before transferring it to alcohol it measured
about 2 mm. in length, but due to its shrinkage while being

FioB. 3S2-3S6,— SectioDi through ■ humui embryo 3 nun. Iodb (No. 361). Enlarved 100 diain«(cn.

Fig. 382, section 27; Fig. 383, 49; Fig. 384. 68; Fig. 385, 76; ud Fig. 386. Bfi. /'A. pharynx; H, tmrt;
UV, umbilioil v«ick; Aa. »on»: C*. chord*; PC. periouduU ealom; P., perilone«l ccFlom: Ejoc..
exoccelom; A., recao rrom pericardial ccclom.

embedded it produced but 160 transverse sections each being 10 1^
thick. The embryo has 7 myotomes. The figures (382-386) show
that the pericardial ccelom encircles the heart on its ventral side
and reaches down into a recess which communicates with the

528 HUMAN EMBRYOLOGY.

peritoneal spaces and through these with the exoeoelom. The
pericardial coelom is entirely closed on all sides. The peritoneal
ccelom is forming at numeroua points in the mesoderm of the
trunk of the emhryo, not in any regular fashion ; some of the
spaces connect irregularly with one another, others connect with
the exoccelom {Fig. 386), as is found to be the case in the sheep.
Dandy has studied this embryo with great care, and a more detailed
account of it, containing also a reconstruction of the coelom, may
be found in his publication.

Quite recently Keibel and Elze described an embryo nearly
2 mm. long in which the pericardial ccelom is separated from the

Fra. 387.— Profile recODstructioD o( an embryo 2.1 mm. looi (No. 12). X 25 times. Am, ajnoicm:
OK, opUc vesicle: Al'., audilory veaick; t/F. umbilical vnide; ff, heart; I'OJtf., omphalomesenteric
veioi nr„ septum tratuvenuni: O*. third occipital myotome; C, eisbth cervical myotome.

exoccelom by a pronounced bridge of tissue. This specimen is of
prime importance in the study of the coelom in the human embryo,
for through it we can connect the development of the ccelom in
older and younger stages with one another, as well as with the
condition found in the rabbit and in the sheep.

Another embryo slightly older shows that the pericardial
ccelom communicates freely with the peritoneal ccelom and this in
turn with the exoccelom (Fig. 387). Probably this specimen is not
altogether normal, because the brain is not well developed and
the spinal cord behind appears to be too wide open. The liver
and thyroid are beginning to form and two branchial pockets are
well developed from the pharynx. In its caudal shifting the
amnion has passed the heart, leaving the ventral body wall cov-
ered with ectoderm. The attachment of the umbilical vesicle

CCELOM AND DIAPHRAGM. 529

to the body is conBtricting from all sides, receding before the
amnion in front, at O, and from the allantots behind, 0'. Some-
what later, when the constriction is more marked and the amnion

Fro. 386.— 8««iOD lhrou«b

had of tlw anbryo Z.I mm. loDi.

tba third oedpit^ myotociB of

X SO tirnn. C». oalom: Pk,

ph»rynx; L. livw, ST. Hvlum

mm. ueuv the tjul thu Fit.

380. X eO timei. C. SrK

ital myotome: C«.oal«a; V,

oervicB] myotome; Cot. ea-

lom; V. [T., umbiliol vdn;

L.. liver; PA. pharynx; UV.

umt»li»lT»ida.

Tuin; [/m*., umbilical vwlde.

Fio. 391.— Section throogh an embryo 3.S Fio. 392. — Section' Ihrouah the embryo 3JS

mm. loDf (No. 164). X GO timm. L. liven f*"'. mm. lone -18 mm. amtnt Uw tail ihaQ Fig. 391.
ventricle ; SR, Noua reunina ; Cot. eat\am. X GO tim«. Cot, ontom ; Int. intntine ; VOM,

omph^onieeentcric vein ; VV,, umbilical vein :

DC ductiu Cuvieri.

comes to iie upon the ombiUcal stalk, VV, the points O and O*
will be the points of commnnication between the peritoneal coelom
of the two sides of the body. Other sections of this embryo are
shown in Fig. 229, Chapter XI.
Vol. I.— 34

530 HUMAN EMBRYOLOGY.

In front the yolk-vein, VOM, connects freely with the capil-
laries of the yolk- vesicle, and as it enters the heart it is bounded
on its ventral side by a recess, Fig. 388, Coe, which, however,
does not communicate directly with the peritoneal ccelom or with
the exocoelom. Capillary veins also arise in the septum trans-
versum, around the liver bud. Fig. 389. More caudal, Fig. 390,
VU, a branch of the vein extends to the lateral side of the body,
which is no doubt the anlage of the umbilical vein. These veins
are more pronounced in an embryo slightly older. Figs. 391 and
392, which shows the ductus Cuvieri, the umbilical vein, the
omphalomesenteric vein, and a vein running from the head — •
the jugular vein. All these veins unite in the sinus reuniens, which
in turn enters the heart.

SEPTUM TRANSVERSUM.

It is seen from the description just given that the body cavities
arise from two primary spaces, as was first well shown by His,
and that each of these in turn is bilateral in origin. In addition
to these there is the exocoelom as well as the cavities of the myo-
tomes which in the human embryo soon disappear ; they communi-
cate in part with the rest of the body cavity (Keibel and Elze).
The two pericardial coelom cavities soon unite at the front end of
the head, and this* space later on encircles the whole ventral sur-
face of the heart. Next, two pockets arise from it, extend dor-
sally, and unite with the two peritoneal cavities. These diver-
ticula barely exist as separate cavities, but blend immediately, as
soon as they begin to form, through the peritoneal cavity with the
exocoelom. By the end of the fourth week, as represented in Fig.
387, the five primitive cavities form a single coelom, from which
at last seven body cavities arise. The primitive and most fun-
damental septum by which the common body cavity is broken into
compartments was discovered by His, which he described as the
septum transversum. Figs. 383 and 384 show that the umbilical
vesicle is probably tied to the heart by means of two blood-vessels,
which are well embedded in a mass of tissue of the embryo as shown
in Fig. 387. Within this mass the blood-vessels go to the heart and
into it the liver grows. To the extent in which the pericardial
coelom (Parietalhohle) does not communicate with the peritoneal
coelom, its floor is formed by a mass of tissue which unites the
two sides of the trunk of the body with each other, and also binds
the sinus venosus to the foregut. It is this mass of tissue which
His terms the primitive diaphragm or the septum transversum.
From it the principal part of the permanent diaphragm is formed,
and by its extension the primary pericardium and the primary
diaphragm are completed.

C(ELOM AND DIAPHRAGM. 531

In an embryo sligbtly larger than. the one just described,
the septum transversum is well defined, as may be seen in Pig. 394.
The lungs have jnst begun to sprout (Fig. 393), and on the right

Fia. 3»a.— .->wIioii <hnius]imn eTiibr)o4.3min. Pia. 304. — S«tion through the tmbtyo 1.3

longiNo.1481. X2!H\aua>. ri.fimt thur«cicmyo- mm. long, A mm, dHper than Fig. 393. X 2S

ach-.B. bmn'chui-; H. heart: T.. thyrmd; i'C', peri- liver; V, 'ventriele : B^ , bulb of the «urla : Am.'.
nntial cavity: L, liver; f IF .. foramen of Winxlow. wtiDiDo: [TV. umbiliol vein.

.side there is a diverticulum from the peritoneal ecelom, which
marks the beginning of the lesser peritoneal cavity. The liver is
beginning to ramify within the septum and
protrudes dorsally into the embryonic per-
itoneal ca\'ity. In another embryo of about
the same age the septum transversum is
practically complete and in its form and
position corresponds exactly with the des-
cription of it given by His (Fig. 395). The
pericardial, pleural, and peritoneal cce-
loms communicate as freely as they ever
will, for there is as yet practically no sign
of the formation of secondary septa. A
reconstruction of the region of the septum
of this embryo, showing the ccelom,is given
in Figs. 396 and 397. The pericardial cav-
ity lies completely on the ventral side of
the septum, from which it extends in the

form of a U-shaped canal around the sep- fio. 3m.— .swi™ nimugh an
turn on either side of the lung, stomach. Muw^vrT »'Hin'a^''vdn';' a.
and intestine. The pleural coelom — that is, ^J!j?Vr''umte'iu^^'«in"^^''
the coelom which surrounds the lung buds

—is much the same in form on both sides of the body, but the
peritoneal co-lom shows marked bilateral inequalities due to the
changes which have taken place with the shifting of the stomach
towards the left side of the body.

632 HUMAN EMBRYOLOaT.

In Fig. 396, below the letters FW, there is a marked depres-
sion, the recessus mesenterico-entericus, which corresponds with
the shifting of the stomach to the left. (This is well shown in
Pig. 405.) Above FW a sac or invagination passes on the dorsal
median side of the lung to form the recessus pnenmato-entericus
dexter. This space also borders upon the liver and forms a
third recess, the recessus hepato-entericus, over the region of the
lobus Spighelii. These spaces together form the lesser peritoneal

Fi«. 3M Mid 307.— Right uid Mt vi
timet. X..aorU; i>A.,pli*r7Sx; fi^.,buib
ITfi, Wolffiu body: S.itomMh; FW. (on

cavity and were recognized as such by His in 1880. From this
time onward it has been described by nmnerous embryologists, and
the most satisfactory study of it in the human embryo is by
Broman, whose terminology I have adopted.

There is but little to be said about the left pleural recess
except that its configuration is that of the Inng over which it
passes. However, between the lung and the stomach (Fig. 397,
L and 8) there is a slight depression. There is present at tliia
point in reptiles and birds a marked pocket, or "left lesser peri-
toneal cavity," which has also been described in maoamalian
embryos by Ravn. Ravn's discovery was doubted by a numl)er

CCELOM AND DIAPHRAGM. 533

of embryologists, but recently Broman has found it in all mam-
malian embryos examined, including the human. According to
Broman the left bursa appears in
human embryos about 3 mm. long,
and vanishes immediately, that is,
before they are 4 mm. long. The
left recessus pneumato-entericus,
as Broman calls it, is decidedly
smaller than the right, does not
encroach upon the left lung as
much as the right does upon the
right lung; in fortunate trans-
verse sections they appear to be i
symmetrical and equal (Fig. 398).
Up to the present stage the
septum transversum, which arose _ «o_b„, .i. .. .i. k, ^

, '^ . o 1 1 T 1 '"*■ ^'"' — Section through the nght uid

m the region of the head, has

gradually receded until its dorsal

end has fallen to the region of the

fifth cervical nerve. This stage

is of importance, for it shows how the phrenic nerve enters the

septum transversum (Fig. 399, Ph). This section shows that the
nerve grows at first between the
subclavian and cardinal veins
along the lateral wall of the pleu-
ral ccelom towards the ductus Cu-
vieri. Subsequently, when the
pericardial ccelom is separated
c. V. from the pleural by the growth of
^*' the pleuroperieardial membrane
from the wall of the ductus Co-
vieri to the root of the lung, it
leaves the nerve on the lateral
edge of this separating membrane.
Later, when the lung burrows to
extend around to the side and the
front of the heart (Fig. 414), the
nerve is pushed into the pleuro-
perieardial membrane between the
F,„ ■i«i_a-..i™,h,™,.*. _„(,™ji»™ heart and the lung. This addi-

F lo. 309. — fMctiOD tnrou^ on onbryo J> nun. ^

loni (No. 80). X 26 tinws. Ct fifth cCTviou tioual rotatiou m the development

nervt; C.V., cardinml v«n; S.. BubclBvi«ji veio; - , . . , ii_ ' __^

DC.ductiuCuTicii: i..iuac: PA, phreoicnerva. 01 tiie viscera moses tnis uerve
the roost important landmark by
which we retain our conception of the relation of these organs.

In addition to the rotation of the organs aromid the phrenic
nerve in the transverse plane of the body, there is another an<j

634 HUMAN EMBRYOLOGY.

greater shifting of the organs in their descent from the region of
the head down into the thorax. This well-known descent of the
diaphragm during development was first observed by von Baer,
and later was more completely studied by His, Uskow, and
myself. The accompanying scheme, Fig. 400, illustrates this
process. On the right side of the schema, which is in the form of
an embryo six weeks old, the numbers of the segments of the body
are given. The space marked Co represents the communication

i
t

2
3
t
S '

5 \ 3

between the pleural and the peritoneal cceloms. The rectangular
blocks in front represent the ])osition of the septura transversum
in embryos of various sizes which are indicated by the accompany-
ing numbers. Thus, the block in the head region represents the
position of the septum in an embryo 2 mm. long and that in the
lower thoracic region the position of the finished diaphragm in an
embryo 24 mm. long. The arrows indicate that the septum is mov-
ing more rapidly where they are located than elsewhere. In gen-
eral there are two main foci aroimd which the diaphragm rotates :

CCELOM AND DIAPHRAGM. 535

{ 1 ) in the upper cervical region at the dorsal end of the septum,
whi<'h is its position in embryos 4 to 7 mm. long, and (2) in the
thoracic region at the ventral end of the septum, which is brought
about by the growth of the heart and lungs within the thorax.

Up to the end of the fiftli week there is no sign whatever of
a separation between the various portions of
the eiplom, but now a line of separation
makes its appearance between the pericardial
and pleural cosloms, due to a constriction of
its walls along the course of the ductus Cu-
vieri, or rather the ductus lies in a ridge of
tissue encircling the canal of communication
between the pleural and the pericardia] cce-
lonis. This ridge is not present in one em-
bryo 5 mm. long, but in another of this size
there is an elevation on the dorsal wall of
the pleural ccelom. Fig. 401, which encircles
the lung and joins the dorsal end of the
septum transversum. This ridge is one of
the pillars of Uskow, or the beginning of the Fia.ioi.-B»gitt»i»eotiiM.
pulmonary ridge, as I have termed it. It k^'(No.'i'3B)°'*>rW*tim«!
gradually widens to cover the whole lung ; on sT'^ii^\;^^^"°L'
its cephalic end it gives rise to the pleuro- '™« ■ ^^""""^ ■*■ ''™ ■
pericardial membrane of Uskow, and on its

caudal end to the pleuroperitoneal membrane of Brachet. For the
present, while it still represents two structures, it should carry a
single name, and I believe pulnionary ridge to be a suitable one. In
later stages, when the pulmonary ridge gives rise to the plearo-
pericardial and the pleuroperitoneal membranes, the name should
be dropped.

SEPARATION OF THE PERICARDIAL, PLEURAL, AND
PERITONEAL CAVITIES.
The first steps required to bring about a separation of these
cavities have been taken and are well under way in an embryo
7 mm. long (Figs. 402-i05). The embryo is well kinked upon itself
and the septum transversum in its wandering is entering the
thorax, as Figs. 400 and 402 show. The communications between
the pericardial and pleural eceloms have been reduced to narrow
slits, as indicated by the arrow in Fig. 402 and in the cast of the
cffilom as shown in Fig. 403. A section through the lung region.
Fig. 404, shows the two ridges cut across four times. The recon-
struction, Fig. 402, gives the relation of the pulmonary ridge to the
surrounding organs and to the structures of the body in its imme-
diate neighborhood. This ridge is well shown in the His Atlas,
embryos A and B, as well as in Piper's reconstruction, and it may

&3e HUMAN EMBRYOLOGY.

be seen in an; human embryo of this stage. The relation of the
ridge to the phrenic nerve, as well as its form in older embryos,
makes of it the anlage of both plenropericardial and pleuroperi-
toneal memhranes. It lies in the sagittal plane of the body in this
embryo in the region of the fourth cervical nerve, immediately
over the iraig bud, and connects the dorsal end of the septum trans-
versum with the Wolffian body. In sagittal sections of embryos
of this stage tbe ridge may also be cut twice, as Fig. 406 shows.

Fra. 402.— Embryo 7

The embryos just described are kinked to their maximum, and
in the next stage, with the disappearance of the sinus pnecervicalis
and the beginning of the development of the neck, the head begins,
to erect itself and the pulmonary ridge widens and spreads both
towards tbe heart and- the stomach, as Fig. 407 shows. The con-
nection between the pleural and pericardial cavities is reduced to
a small narrow slit, which is guarded on the pericardial side by
a valvfr-like membrane, the pleuroperieardial membrane.

As the pulmonary ridge widens to encircle most of the lung,
the dorsal end of the septum transversum sinks into the thorax

CtELOM AMD DIAPHRAGM.

It or oieIodi of the snbryo 7 mm. Fio. 404,— Bection thraush t1

a. P., p«ric«fdUl oceIoed; Z,„ stoment of the embryo 7 mm. k
liver: W.B., pontion o\ Wolffian timn. Ct. seventh cervical my<
dinalvdn; D.C.. cIueUu Cuvii
plexua; PR., pulmonary ridge; ,
fi.. broDcfaus: //.heart: B.A.,\

rough the embryo T mm. Fio. 406.— Section through an embryo fl.S m

1 404. X 25 limn. T\. long (No. IIS). X 26 times. Ph. pharynx:

:'.V., ardiual vein: tr.fi.. arm; PA., pulmonary ridge; £, Iudr.
h; LPCJeeserpehloneal
S.r.eeptum iraneveisum.

more rapidly than does its ventral end. By this process the septum
gradually turns a half revolution. The side that was its ventral
surface in an embryo 7 mm. long (Fig. 402) has become its dorsal
surface in an embryo 11 mm. long (Fig. 414). All this is well

HUMAN EMBRYOLOGY.

Fin. Wr— KmbryoOm

Fig. «8,-S»ftioii through the filth ccrviml

Fi

o. ««.— Secli

on .Ifl mm. lower than Fig. 408.

myotome of tlia almvB embryt., X 12 tjni«. Cv.

tinxii. C, ,

fifth myolomer V.C., cardinal vein; D.C.. dumu,-

cMin

al vein; Ph..

phrenic ner.-e; F.C^ pleur.^

Cuvieri; fir., brochial plesus: PA., phrenic nene;

rdiBl membnir

le: PP., pleuroperiloneBl m«n.

brane;

PI. (■«.. pleii

ilie beginning of the pleuropericardiil membrane.

cu'lom

shown in the three reconstructed figures as well as in the dingrain
(Fig. 400). As the pulmonarj' ridge widens, the lung buds become
buried deeper and deeper in the body walls of the embryo, and as
the liver gradually shifts with the rotation of the septum, the
lungs are forced, step by step, to the side of the septum opposite

CtELOM AND DIAPHRAGM. 539

the liver {Fig. 414). So, therefore, the lung which was in contact
with the liver is shifted to the upper side of the septum by the
widening of the pulmonary ridge and by the more rapid rotation
of the dorsal end of the septum which carries the liver ventral-

.w.a.

-. IF.S., Wolffimi body.

Fia. 412. — Sagittal Hction ihnnigh ui ffubryu Fia. 413. — Section Ihrough t

8 mm. long (No. 113). X 10 limeg. J, lower ja»: wbich Fix. 412 i> taken, nearer
K. Prat. liDiu pivcervicalio : 4. fourth cervical

veraum: IM'. ducliu Cuvicri; P,C.. pleuropericsr-
dial mcmbnne: PP.. pleuruperitonfal membranp:
.S.. alomnch; i.P.C, leswr peritoneal cavity; »'.
S^ Wolffian body.

The sections of the embryo pictured in Fig. 407 are shown in
Figs. 408-411. They do not include the communication between
the pleural and pericardial coeloms. However, they show the posi-
tion of the phrenic nerve, and this, because of its later position,
indicates the extent of the pleuropericardial membrane. In Fig.
409 a cavity is seen dorsal and lateral to the pleural coelom, and

540 HUMAN EMBRYOLOGY.

this burrowing continues until it approaches the pericardial coelom,
where a new membrane is formed, the membrana pericardiaco-
peritonealis. This membrane is farther emphasized when the
liver begins to separate from the septum transversum, leaving but
a thin membrane between the pericardial and peritoneal cceloms.

Figs. 412 and 413 are from sagittal sections of an embryo
about as large as the one pictured in Fig. 407. The phrenic nen'e
is shown throughout its whole course, from the fifth een'ical nerve
to the pleuropericardial oiembrane. Hanging from the pleiiro-
pericardial membrane a section of the pleuroperitoneal may be

— Kmbryo 1 1 mm.

seen {Fig. 412), which extends around the lung and unites with
the dorsal body wall (Fig. 413) immediately in front of (he
WolflSan body. About this time that portion of the pulmonary
ridge destined to become the pleuropericardial membrane unites
with the root of the lung and separates the pericardial space com-
pletely from the pleural. All this has just taken place in an
embrj'o 11 mm. long and is shown in Figs. 414, 415, and 416. The
plane of the pi eurojieri cardial membrane is now practically that of
tlie septum transversum, the two together being transverse to the
long axis of the embryo. The course of the ductus Cuvieri is
along the edge of the pleuropericardial membrane, and that of
the phrenic nerve is well within it (Fig, 416).

C(ELOM AND DIAPHRAGM. 541

The relation of the ductns Cuvieri to the point of closure
between the pleural and pericardial cavity was first pointed out

Fio. 415. — Section tbroush ths body of the Fia.416. — Section Chnnigh the mnevmbryo. 18

MinievnbrvosbinrniD Fir 414, X lOtimn. Ph., mm.low«thuFi|. 41G. X lOtimai. PA.phnoio

phroilii nerve; PC., pleuropericudial membnue: nerve; S.T., septum tnDBvanum: PC., plmiroperi-

5.7*.. septum tnnsvereum; H.. bumenu; 1. 2. wrdiftl membnuie; PP., ideuroperitoneal mau-

3. rib*. brane; I. 2. 3, 4, nbs.

by His in 1881, and since then little has been added to our knowl-
edge of the process by which the separation is made.

At the time of the closure the
small ridge of tissue called the pleu-
ropericardial membrane (Uskow) is
very insignifieant,its extension being
due to a subsequent rapid growth of
the lung. It is, however, to the cred-
it of Braehet to have shown that the
canal connecting the pleural and
pericardial cavities is oijy constrict-
ed by the ductus Cuvieri, and that its s
complete closure is due to the active ^
growth of the aulage of the pleuro-
pericardial membrane.

After the pericardial cavity is
fully isolated the pulmonary ridge
spreads out rapidly over the lung
buds (Fig. 414) and forms an incom-
plete membrane at its lower tip,
through which the pleural and peri-
toneal cavities communicate for some

time longer. This membrane — the pleuroperitoneal membrane of
Braehet — soon forms a-<-shaped figure, with the pleuropericardial

Fro. 417.— 1

toctioD .46 mm. lower thu

Rb. 416. X 1

S42 HUMAN EMBRYOLOGY.

membrane aboA-e and the septum transversum on its ventral side.
On its dorsal it is closely related to the Wolffian body, whose de-
scent it follows closely. Before this membrane is completed there
must be added to it the ridge of tissue from the septum transver-
sum to the Wolffian body, described by Uskow as the dorsal pillars

of the diaphragm. The true nature of these pillars and their re-
lation to the permanent diaphragm was finally determined by Ravn
and Brachet, and by Swaen for the human embryo.

In a human embryo 11 mm. long, immediately after the com-
pletion of the pleuroperieardial membrane, it is seen that the rota-
tion of the liver and septum transversum is accelerated, and that

the pleuroperitoneal membrane extends rapidly down into the
thorax as the Wolffian body recedes. (Compare Figs. 407 and 414.)
The -^-shaped section of the septum transversum and
pleuroperieardial and peritoneal membranes (Fig. 414) is soon
changed by the growth of the lung and the shifting of the dia-
phragm (Figs. 417 and 418), which gradually places the pleuro-
perieardial membrane at right angles to the diaphragm. The
opening behind the pleural and peritoneal cavities gradually

CCELOM AND DIAPHRAGM. 5^S

becomes smaller and smaller (Fig. 419), closes first on the right
and then on the left side (Fig. 420) ; usually both membranes are
complete in embryos 19 nam. long.

As the lungs invade the thorax in the wandering of the dia-
phragm they must carry their surrounding pleural space with
them, which calls for a radical shifting of the mesenchyme between
the parietal pleura and the ribs. In fact there is a great mass of
mesenchyme just at this point (Figs. 417 to 420), which in embryos
at this stage has many unusually large spaces in it indicating that
they are normal tears. After the diaphragm has reached its
permanent position and the lungs begin to grow relatively larger,
they encroach upon this tissue and it is reduced in quantity to
make room for them. The lung also burrows between the pleuro-
pericardial membrane and the main body wall, increases the
extent of the membrane, and pushes it with its inclosed phrenic
nerve to the medial side of the lung, between it and the heart.

To what extent the permanent diaphragm is formed from
the pleuroperitoneal membrane is difficult to determine. It is
probable that the portion dorsal to the attachment of the pleuro-
pericardial membrane of the septum transversum is formed by
the pleuroperitoneal membrane. At any rate, the point of entrance
of the phrenic nerve may be viewed as the most fixed point, one
difficult to shift, for it is closly associated with the muscle of the
diaphragm which invades the septum transversum when it is still
high in the neck of the embryo. However, this kind of reasoning
is not altogether sound and should be taken with some reserve.
The shifting of large masses of organs, their power to burrow
and extend as the lung does around the heart, and the fact that
the liver grows into the pleuroperitoneal membrane (Fig. 418)
while it is being separated from the septum transversum on its
ventral side (Fig. 417), should make us somewhat reserved in our
statements regarding the origin of the dorsal and ventral dia-
phragms. In reality we have gotten but a little further than to
confirm His, who stated that the septum transversum is extended
dorsally and separates the pleural from the pericardial and peri-
toneal cavities. Defining the septum transversum as he did,
proved to be the foundation-stone of all subsequent study regard-
ing the separation of the body cavities.

The coelom cavities of the myotomes are in general inde-
pendent of the peritoneal cavity in man, with the exception of the
second, which, according to Keibel and Elze, communicate with
this cavity in an embryo 1.38 mm. long. These cavities of the
myotomes are well developed in embryos 2 mm. long, but after this
stage they soon disappear.

The diverticulum of the coelom into which the testis wanders
begins to form as the Wolffian body atrophies during the third

544 HUMAN EMBRYOLOGY.

month of pregnancy. At first there is an evagination of the
abdominal wall in the inguinal region^ forming the inguinal bursa^
which is lined by a sac of peritoneum, the vaginal process. This
in turn sinks into the embryonic scrotum, which has formed inde-
I)endently. Soon the bursa is partly filled again by a marked
thickening of its apex to form the conus inguinalis or gubemacu-
lum, which continues into the genito-inguinal ligament to the testis.
During the seventh month the final descent of the testis takes
place. At this time the bursa becomes markedly enlarged, the
conus retracts, and the testis moves into the embryonic tunica
vaginalis, which becomes completely separated from the peritoneal
cavity at about the time of birth.

A similar but much less marked process takes place in the
female. In the case of the ovary the migration is slight, although
provision for the descent has been made in the formation of both
inguinal bursa and ligament. The lumen of the vaginal process
usually disappears, but may remain open to form what is known
as the diverticulum of Nuck.

In not all cases does the testis enter the inguinal bursa, but
instead remains in the abdominal cavity or within the inguinal
canal. In other cases the processus vaginalis does not close after
the descent of the testis and some of the abdominal viscera may
enter the canal, forming congenital inguinal hernia. A similar
hernia of the diaphragm may occur when the communication
between the pleural and peritoneal coelom is not completely cut off.
This kind of anomaly is much more common in the left side of the
body than on the right, probably on account of the corresponding
unequal growth of the liver on the two sides of the body. Con-
genital hernia may also occur in the umbilical cord when the
coelom of the cord is not obliterated after the intestine returns
from it into the abdominal cavity. In case the opening with the
exoccelom of the cord is very large, most of the abdominal viscera
— liver, spleen, large and small intestines — may extend into it.
In such cases the extruded viscera are covered only by a thin
membrane composed of peritoneum and amnion.

There remains still one very fundamental pocket of the peri-
toneal coelom; it is, the pocket which forms the lesser peritoneal
cavity. This pocket, the bursa omentalis, was first recognized in
the embryo by His, and later Ravn discovered that it developed
not only on the right side of the body but on the left side also,
and that the cephalic tip of the right cavity separated and formed
one of the serous spaces which comes to lie in the region of the
right lung. More recently the development of the lesser peritoneal
cavity in man has been studied by Swaen and by Broman.
Broman's admirable study is comparative and includes numerous

C<ELOM AND DIAPHRAGM. 54S

human embryos; he confirms for the human embryos Bavn's dis-
coveries in the rabbit, mentioned above.

In an embryo 3 mm. long there are two peritoneal pockets on
either side of the oesophagus, the right being somewhat larger
than the left. The left is of but short duration in the human
embryo; it evaginates, Broman believes, but the right, the reeesaus
pneumato-entericus dexter, is
plosely associated with the less-
er peritoneal cavity. Just be-
low this recess there is another
depression (Fig. 396, below
FW), the recessus mesenterico-
enterieus of Swaen, which soon
extends between the stomach
and liver and later gives rise to
the omental bursa.

A reconstruction of the
right recess, in an embryo 5 "'
mm. long, is shown in Fig. 421.
The upper recess (Bpedx)
reaches to the lung bud of the
right side, the dorsal recess ex-
tends into the mesentery of the
stomach, and the ventral recess,
recessus hepato-entericus, bor-
ders on the liver and later en-
circles the Spighelian lobe. Be-
low they communicate with the
peritoneal cavity through the
hiatus communis recessuum
(Her) or the primitive foramen
of Winslow. Sections throuch

,, ,. , , • i.1 Fia. «l.— Caat of the le*Br peritopeal Mvity

the hiatus maV be seen m three Bncirelmgtheinte5tine.froinahunuuien.biyo5rain.

different stages in Figs. 393, i^^t^ri^ld^w^^'.-^'^il^^ri^^!^!^

405, and 411. As the stomach «">; fi**., recewus hepew-entericus: ffcf.. hLMiM

grows and bends to the left, it ™""" "'"

gradually gives form to the lesser peritoneal cavity, as is shown
by a cast of it from an embryo 11.7 mm. long {Fig. 422). It is
easily seen that the hiatus of Fig. 421 has become the true foramen
of Winslow, the recessus hepato-entericus has become the cavity of
the lesser omentum (Bomin), and the recessus mesenterico-enteri-
cus has become the cavity of the greater omentum (Bomaj). The
cavity of the greater omentum is formed, according to Swaen, by
a burrowing of the cavity into the wall of the stomach, and not by
a simple bend of its mesentery, as is indicated, for instance, in Fig.
411, According to the B.N.A., the bursa omentalis is divided into
•-- Vol. I.— 35

M6 HUMAN EMBRYOLOGY.

a vestibulum and a recessus superior, which form together Bro-
man's bursa omenti minoria, and a recessus inferior, which is the
same as the bursa omenti majoris. In my opinion, it would be
better to apply the terms of the B.N.A. to these spaces in the
embryo as soon as their fate is clear. For the same reason I
have used the term pericardia] cavity in describing the smallest
embryos, for the relation of this space to the heart enables us to
identify it. Additional unnecessary names only complicate the
subject.

According to Broman, the recessus pneumato-entericus of
Eavn extends upward in tlie human embryo to the bifurcation of
the lungs. By the time the embryo is 11 mm. long, the recessus
pneumato-entericus begins to separate from the lesser peritoneal
cavity and is soon pinched off to form the bursa infraciirdiaca, as
sliown in Fig. 422. From now on, it can be found in all embryos
as a closed sac lying between the right side of the cesophagus and
the diaphragm. It gradually grows in size and is about one centi-
metre in diameter at birth; in a specimen from an adult man
(Fig. 423, Bic) it measures 42 x 20 mm. This third pleural cavity,
very well developed in all animals which have an infracardial lol>e
of the lung, is therefore found in all human embryos and probably
also in most adults. Its frequency will have to be established by
statistics.

CCELOM AND DIAPHRAGM. 547

The various body cavities eommuQieate freely with one
another in all vertebrate embryos. In later stages this primitive
cavity is divided into several compartments by the formation of
the septa described above. Only in Myxine does it remain single,
while in Petromyzon the division takes place at the time of meta-

In selachians the pericardial cavity becomes separated com-
l)letely from the remaining peritoneal cavity by the septum peri-
cardiacoperitoneale. This membrane is present also in ganoids
imd teleosts, but as yet it has not been studied carefuUy, -

Indejjendent pleural cavities are not found in amphibians nor
in most reptiles; in birds, however, there is alwaj's a complete
pleuroperitoneal merabnme present. The process of the sub-
division of the ccelom is far more complex in mammals than in
the remaining vertebrates. In them the septum pericardiaeo-
peritoneale is called the septum transversum, from the dorsal end
of which both the plenropericardial and pleuroperitoneal mem-
branes arise, A chief difference between mammals, on the one
hand, and birds, reptiles, amphibia, and fishes, on the other, is
the very early formation of the septa in the former and their late
appearance in the latter.

LITERATURE.

Bonnet: Beitriige ziir Embryologie der Wiederkauer, Arch, fiir Anat. und Phyaiol,,

Anat. Abl., 1889.
Bbaciiet: Die Eiitwicklung der grossen Korperfaohlen und ihre Trennung vonein-

ander, Ergebnisse der Anat. und Entwicklungsgescb., Bd. 7, 1897.
Bulletin de I'Aead^mie Royale de M^decine. Vol, lix. Broxelles, 1906.

548 HUMAN EMBRYOLOGY.

Broman : Beschreibimg eines menschlichen Embryo von beinabe 3 mm. Lange,

Morpbol. Arbeiten, Bd. 5, 1894.
Entwickliing des Zwerchfelles beim Menscben, Verhandl. d. anat. Gesellscb.,

1902.
Die Entwickluiigsgeschichte der bursa omentalis, Wiesbaden, 1904.
Bryce and Teacher: Contribution to the Study of the Early Development and

Imbedding of the Human Ovum, Glasgow, 1908.
Dandy: A Human Embryo with Seven Pairs of Somites, Measuring About 2

mm. in Length, Amer. Jouni. of Anatomy, vol. 10, 1910.
Herzog : Contribution to Our Knowledge of the Earliest Known Stages of Placen-

tation and Embryonic Development in Man, Amer. Joum. of Anatomy, 1909.
His: Anatomic der menschl. Embryonen, Heft 1, 1880.

Mitteilung zur Embryologie der Siiugetiere und des Menschen, Arch. f. Anat.

u. Physiol., Anat. Abt., 1881.
Hochstetter: Die Entwicklung des Blutgefass-Systems, Hertwig's Handb. d.

vergleich. und exper. Entwickl. d. Wirbeltiere, Bd. 3, 1906.
Keibel : Menschenaflfen, IX. Lieferung von Selenka's Werk, Wiesbaden, 1906.
Keibel und Elze: Normentafeln zur Entwickl. d. Wirbeltiere (Mensch), Heft 8,

1908.
Klaatsch : Uber den descensus testiculorum, Morph. Jahrbuch, Bd. ] 6, 1890.
Kolliker: Entwicklungsgeschichte des Menscben, Leipzig, 1879.
Mall: Development of the Lesser Peritoneal Cavity in Birds and Mammals,

Joum. of Morphol., vol. 11, 1891.
Development of the Human Coelom, Journ. of Morphol., vol. 12, 1897.
Supplementary Note on the Development of the Human Intestine, Anat. Anz.,

Bd. 16, 1899.
Contribution to the Study of the Pathology of Human Embr>'o, Johns Hopkins

Hospital Rep., vol. 9, 1900, and Joum. of Morph., vol. 19, 1908.
On the Development of the Human Diaphragm, Johns Hopkins Hospital

Bulletin, vol. 12, 1901; and Proceedings of Amer. Assoc. Anatom., vol. 5,

Washington, 1901.
Mazilier: Contribution de Pembryologie du diaphragma, Lille, 1907.
M15LLER, E. : Beitrage der Anatomic des menschlichen Fetus, Kgl. Schwedisebe

Akademie, Bd. 29, 1897.
MuLLER, L: Uber den Ursprung der Netze, Meckel's Arch., 1830.
Piersol: Human Anatomy, Philadelphia, 1907.
Piper: Tiber ein im Ziegler'schen Atelier hergestelltes Modell eines menschlichen

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